JKU

The ALPL Gene Variant Database

OMIM *171760



Welcome to the ALPL gene mutations database. This site has been compiled to provide up-to-date information about genetic variation of the ALPL gene responsible for hypophosphatasia.

Hypophosphatasia (MIM 146300, 241500, 241510)

The ALPL gene (also called TNSALP; ID:249; MIM 171760), is localized on chromosome 1p36.12 and encodes tissue nonspecific alkaline phosphatase (TNSALP). Pathogenic loss of function mutations in ALPL cause hypophosphatasia (HPP), a rare, multisystemic condition that decreases mineralisation of bones and teeth and causes early loss of baby teeth, muscle weakness and joint pain. In its most severe, recessively inherited perinatal and infantile forms, which untreated have a very high mortality, HPP is also associated with pulmonary hypoplasia with respiratory failure, vitamin B6 responsive seizures, failure to thrive, craniosynostosis and severe rickets-like features. HPP can present or manifest at any age since the phenotypic spectrum is a continuum. Traditional classification into prenatal benign (ORPHA247638), perinatal lethal (ORPHA 247623), infantile (ORPHA 247651), childhood (ORPHA 247667), adult (ORPHA 247676) and odonto HPP (ORPHA 247685) is under debate. The prevalence of severe forms is low (estimated at 1/300,000 in Europe, 1/100,000 in North America), whereas less severe forms are more frequently observed (estimated at 1/6000 in Europe).

Low serum alkaline phosphatase (ALP) is a hallmark diagnostic feature of HPP. However, the condition requires genetic confirmation since ALP can be low for various reasons.(Saraff et al, 2016, Riancho-Zarrabeitia et al, 2016)

The global HPP registry is collecting real-world data to capture the phenotypic spectrum, natural course of disease and the response to enzyme replacement therapy with asfotase alfa. Other approaches, such as gene therapy, are currently being investigated (Ikeue et al. 2018, Nakamura-Takahashi A et al 2020). For more information on HPP, also consult Orphanet.



ALPL
gene variants

More than 400 ALPL variants have been identified which are responsible for the extraordinary clinical heterogeneity. A clear but imperfect genotype-phenotype correlation has been observed, suggesting that other genetic or environmental factors modulate the phenotype.

According to ACGM criteria, variants can be classified into benign (1), likely benign (2), unknown significance (3), likely pathogenic (4) and pathogenic (5). This database aims to assist physicians, geneticists, researchers and anyone with interest in HPP to retrieve the most detailed and up-to-date of information on every ALPL variant described to date.

Until January 2021, this site was hosted by the University of Versailles (Prof Etienne Mornet). Our new site at the Johannes Kepler University Linz, Austria (JKU) builds on this work and strives to provide continuously updated, detailed variant-specific data on ALPL genotypes and associated phenotypes, variant classification according to ACGM criteria and in-vitro enzyme activity compared to wild type, as well as information on dominant negative effects.



The HPP gene variant consortium

Prof Wolfgang Högler leads a consortium of researchers, endocrinologists, osteologists, basic scientists and geneticists. The consortium meets regularly to assess research results from in-vitro testing in order to re-classify variants. The Members are: Priya Kishnani; Catherine Rehder; Cheryl Rockman-Greenberg; Kathryn Dahir; Gabriel Martos-Moreno; Agnes Linglart; Keiichi Ozono; Eric Rush; Severine Bacrot; Lothar Seefried; Guillermo del Angel; Gerald Webersinke; Ahmed El-Gazzar; Wolfgang Högler (Consortium Lead, JKU Linz, Austria).

Submission of new variants and functional testing of VUS

Our research lab at JKU Linz, Austria has the capacity and the funding (externally sponsored research agreement, Alexion Pharmaceuticals, Inc) to conduct functional testing of VUS submitted to us. Clinicians and geneticists are encouraged to report any new ALPL variant to this site and thereby assist us in keeping it complete and up-to-date.

For submission of variants, please contact Email: HPPresearch@jku.at



Table of mutations

Exon Base change
Amino acid change

(standardized nomenclature)

Pathogenicity

Amino acid change

(Non standardized nomenclature)


Reference
Clinical form of the patient Genotype of the patient


Residual activity

Dominant negative effect
Conservation
%
WT
reference
% 50/50
reference
1 c.-195C>T P Taillandier et al. 2000 perinatal c.[-195C>T];[602G>A] na
2 c.3G>A p.Met1Ile LP Met-17Ile Mentrup et al. 2011 adult c.[3G>A];[?] 1.0 Mentrup et al. 2011 59.0 Mentrup et al. 2011 ++
2 c.17T>A p.Leu6* P Leu-12Ter Taillandier et al. 2000 childhood c.[17T>A];[?] na
2 c.18del p.Val7Tyrfs P Val-11Tyrfs Cui et al. 2012 infantile c.[18del];[407G>C] na
2 c.29T>C p.Ile10Thr P Ile-8Thr Versailles lab June 2017 infantile c.[29T>C];[29T>C] 29.2 del Angel et al. 2020 64.9 del Angel et al. 2020 +
2 c.41T>C p.Leu14Pro Leu-4Pro Versailles lab Jul 2010 adult c.[41T>C];[571G>A] +
2 c.46_49del p.Asn16Profs pAsn-2Profs

Versailles lab March 2011

de Roo et al. 2014

infantile

infantile

c.[46_49del];[668G>A]

na
2 c.50C> T p.Ser17Phe P Ser-1Phe Mornet et al. 1998 infantile c.[50C> T];[223G>A] 19.0 Zurutuza et al. 1999 +
2 c.61G>A p.Glu21Lys P Glu4Lys Research center for
medical genetics, Moscow,
Apr. 2015
adult c.[.61G>A];[?] ++
IVS2 c.62-1G>A Versailles lab Feb. 2019 adult c.[62-1G>A];[=] na
IVS2 c.62-1G>C P Versailles lab March 2013 perinatal na
3 c.69_74del p.Glu4_Lys5del Versailles lab May 2012 perinatal c.[69_74del];[146A>T] na
3 c.82T>G p.Tyr28Asp P Tyr11Asp Yang et al. 2013 odonto c.[82T>G];[1162T>C] 0 Yang et al. 2013

45

Yang et al. 2013 ++
3 c.83A>G p.Tyr28Cys P Tyr11Cys

Taillandier et al. 2001

infantile

c.[83A>G];[407G>A]

7.2 Taillandier et al. 2001 ++
3 c.85T>C p.Trp29Arg P Trp12Arg Chen et al. 2017 childhood c.[85T>C];[1559del] 4.1 Chen et al. 2017 33.7 Chen et al. 2017 ++
3 c.88C>T p.Arg30* P Arg13Ter Versailles lab Dec 2010 perinatal c.[88C>T];[385G>A] na
3 c.94C>T p.Gln32* Gln15Ter Versailles lab. Apr 2011 perinatal c.[94C>T];[648+1G>A] na
3 c.97G>C p.Ala33Pro Ala16Pro University of Brasilia Lab,
July 2016
infantile c.[97G>C;112A>G];[1307A>G] +
3 c.98C>T p.Ala33Val P Ala16Val


Henthorn et al. 1992

Reis et al. 2020

childhood

infantile

c.[98C>T];[1306T>C]

c.[98C>T];[98C>T]

12.0 del Angel et al. 2020 62.6 del Angel et al. 2020 +
3 c.106A>C p.Thr36Pro Thr19Pro Versailles lab Nov 2008 perinatal c.[106A>C];[106A>C] ++
3 c.110T>C p.Leu37Pro P Leu20Pro

Versailles lab oct. 2003

del Angel et al. 2020

perinatal c.[110T>C];[110T>C] ++
3 c.[113_116del ; 118_119insG] p.Lys38_Tyr39delinsMet p.Lys21_Tyr22delinsMet Versailles lab Dec. 2017 adult c.[113_116del;118_119insG];[=] na
3 c.119C>T p.Ala40Val P Ala23Val

Mornet et al. 1998

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

perinatal

perinatal

perinatal

infantile

infantile

c.[119C>T];[1417C>T]

c.[119C>T];[1172G>A]

c.[119C>T];[395C>T]

c.[119C>T];[746G>T]

c.[119C>T;[1142A>G]

2.3

6.9

Zurutuza et al. 1999

del Angel et al. 2020

51.3

87.0

Lia-Baldini et al. 2001

del Angel et al. 2020

+
3 c.129del p.Gln44Argfs P Gln27Argfs Whyte et al. 2015 childhood c.[129del];[1307A>G] na
3 c.130C>T p.Gln44* P Gln27Ter

Mornet et al. 2020

perinatal

c.[130C>T];[662dup]

na
3 c.140A>T p.Asn47Ile Asn30Ile Saglam et al. 2017

perinatal

adult

c.[140A>T];[140A>T]

c.[140A>T];[=]

++
3 c.146A>T p.Asn49Ile Asn32Ile Versailles lab May 2012 perinatal c.[69_74del];[146A>T] +
3 c.151G>T p.Ala51Ser P Ala34Ser Mumm et al. 2002 infantile c.[151G>T];[400_401delinsCA] ++
3 c.152C>T p.Ala51Val P Ala34Val

Taillandier et al. 2001

del Angel et al. 2020

infantile

perinatal

c.[152C>T];[1375G>A]

c.[152C>T];[152C>T]

4.4 del Angel et al. 2020 52.3 del Angel et al. 2020 ++
3 c.165_167del p.Ile55del LP Ile38del del Angel et al. 2020 perinatal c.[165_167del];[648+1G>A]
3 c.178G>C p.Asp60His VUS Asp43His McKiernan et al.2017 asymptomatic* c.[178G>C];[=]
3 c.180T>G p.Asp60Glu P Asp43Glu Whyte et al. 2015 childhood c.[180T>G];[=] ++
IVS3 c.182-2A>C P Whyte et al. 2015 childhood c.[182-2A>C];[=] na
IVS3 c.182-3C>A Mornet et al. 2020 infantile c.[182-3C>A];[407G>A] na
4 c.184A>T p.Met62Leu P Met45Leu Taillandier et al. 1999 infantile c.[184A>T];[1172del] 27.4 Zurutuza et al. 1999 ++
4 c.184A>G p.Met62Val P Met45Val Spentchian et al. 2003 infantile c.[184A>G];[184A>G] ++
4 c.186G>C p.Met62Ile P Met45Ile Taillandier et al.2005 childhood c.[186G>C];[571G>A] 0 Taillandier et al.2005 ++
4 c.187G>C p.Gly63Arg P Gly46Arg Spentchian et al. 2003 infantile c.[187G>C];[187G>C] ++
4 c.187_205del19 p.Gly63Leufs

Versailles lab Jan 2010

Taillandier et al. 2017

adult c.[187_205del];[=] na
4 c.188_205dup18 p.Gly63_Thr68dup P Guanabens et al. 2013 adult c.[188_205dup18];[?] na
4 c.188G>T p.Gly63Val P Gly46Val Lia-Baldini et al. 2001 infantile c.[188G>T];[=] 0.8 Lia-Baldini et al. 2001 26.0 Lia-Baldini et al. 2001 ++
4 c.194C>A p.Ser65Tyr Ser48Tyr Saglam et al. 2017 perinatal c.[194C>A];[194C>A]
4 c.203C>T p.Thr68Met P Thr51Met

Orimo et al. 2002

Mao et al.2019

del Angel et al. 2020

del Angel et al. 2020

childhood

childhood

perinatal

adult

c.[203C>T];[529G>A]

c.[203C>T];[571G>A]

c.[203C>T];[814C>T]

c.[203C>T];[=]

5.2

3.0

Orimo et al. 2001

del Angel et al. 2020

36.7 del Angel et al. 2020 ++
4 c.202_204del p.Thr68del Thr51del communicated by S. Lazarus,
Royal Brisbane &Women's
Hospital, Herston, Australia
adult c.[202_204del];[=] na
4 c.208G>A p.Ala70Thr VUS Ala53Thr communicated by Dr S. Brugge
r and T. Brown (Alexion)
Mild form. Patient with low AP and unspecific symptoms c.[208G>A];[208G>A] +
4 c.211C>T p.Arg71Cys P Arg54Cys

Henthorn et al. 1992

del Angel et al. 2020

infantile

odonto

c.[211C>T];[811A>C]

c.[211C>T];[=]

0

7.7

Fukushi-Irié et al. 2000

del Angel et al. 2020

35.0

33.2

Fauvert et al. 2009

del Angel et al. 2020

++
4 c.211C>G p.Arg71Gly P Arg54Gly

Research center for medical
genetics, Moscow, June 2015

Tenorio et al. 2017

adult

childhood

c.[211C>G];[=]

c.[211C>G];[=]

++
4 c.211C>A p.Arg71Ser P Arg54Ser Orimo et al. 2002 childhood c.[211C>A];[?] 2.9 Orimo et al. 2001 ++
4 c.212G>C p.Arg71Pro P Arg54Pro Henthorn et al. 1992 perinatal c.[212G>C];[620A>C] 4.1 del Angel et al. 2020 59.8 del Angel et al. 2020 ++
4 c.212G>A p.Arg71His P Arg54His

Taillandier et al. 2001

Mao et al.2019

Reibel et al. 2009

perinatal

childhood

odonto

c.[119C>T];[212G>A]

c.[212G>A];[571G>A]

c.[212G>A];[=]

1.0

6.6

Fauvert et al. 2009

del Angel et al. 2020

30.5

32.5

Fauvert et al. 2009 ++
4 c.215T>C p.Ile72Thr P Ile55Thr Versailles lab oct. 2004 odonto c.[215T>C];[=] 5.1 Fauvert et al. 2009 40.2 Fauvert et al. 2009 ++
4 c.214A>G p.Ile72Val Ile55Val Versailles lab dec. 2014 infantile c.[214A>G];[214A>G] ++
4 c.217_219del p.Leu73del Leu56del

Versailles lab aug. 2013

Tenorio et al. 2017

asymptomatic*

childhood

c.[217_219del];[=]

c.[217_219del];[=]

na
4 c.223G>A p.Gly75Ser P Gly58Ser Mornet et al. 1998 infantile c.[50C> T];[223G>A] 3.5 Zurutuza et al. 1999 ++
4 c.227A>G p.Gln76Arg P Gln59Arg

Mornet et al. 2001

del Angel et al. 2020

infantile

infantile

c.[227A>G];[401C>A]

c.[227A>G];[571G>A]

3.0 del Angel et al. 2020 39.8 del Angel et al. 2020 ++
4 c.228G>T p.Gln76His P
4 c.228del P Li et al. 2017 infantile c.[228del];[407G>A] na
4 c.242del p.Pro81Leufs Pro64Leufs

Versailles lab Jul 2009
del Angel et al. 2020

perinatal c.[242del];[242del] na
4 c.247G>T p.Glu83* Glu66Ter Versailles lab Apr 2011 infantile c.[247G>T];[247G>T] na
4 c.251A>T p.Glu84Val P Glu67Val Wei et al. 2010 odonto c.[251A>T];[?] +
4 c.252G>C p.Glu84Asp Glu67Asp Whyte et al. 2016 infantile c.[252G>C];[1375G>A] +
4 c.262G>A p.Glu88Lys P Glu71Lys Mohn et al. 2011 infantile c.[262G>A];[920C>T] ++
4 c.277C>T p.Pro93Ser P Pro76Ser Peach et al. 2007 prenat. benign c.[277C>T];[400_401delinsCA] 70.0 del Angel et al. 2020 121 del Angel et al. 2020 ++
4 c.283G>A p.Val95Met P Val78Met Versailles lab Sept 2019 adult c.[283G>A];[=] 56.8 del Angel et al. 2020 79.6 del Angel et al. 2020 ++
4 c.297G>C p.Lys99Asn Lys82Asn Seefried et al. 2017 adult c.[297G>C];[=] ++
IVS4 c.297+2T>A Clinvar (Counsyl) infantile not provided na
IVS4 c.297+3G>T LP Versailles lab. Jan 2011 infantile c.[297+3G>T];[299C>T] na
IVS4 c.298-2A>G P

Taillandier et al. 2000

Versailles lab

Versailles lab

perinatal

perinatal

odonto

c.[298-2A>G];[997+3A>C]

c.[298-2A>G];[407G>A]

c.[298-2A>G];[=]

na
IVS4 c.298-1G>A P Zhang et al. 2012 adult c.[298-1G>A];[298-1G>A] na
5 c.299C>T p.Thr100Met P Thr83Met

Mornet et al. 2001

del Angel et al. 2020

Michigami et al.2020

Taillandier et al. 2015

Maman et al. 2016

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

infantile

adult

perinatal benign

perinatal

adult

perinatal

perinatal

childhood

c.[299C>T];[571G>A]

c.[299C>T];[571G>A]

c.[299C>T];[982T>C]

c.[299C>T];[1258G>A]

c.[299C>T];[571G>A]

c.[299C>T];[227A>G]

c.[299C>T];[299C>T]

c.[299C>T];[=]

1.3

5.8

Fauvert et al. 2009

del Angel et al. 2020

28.2

32.4

Fauvert et al. 2009

del Angel et al. 2020

++
5 c.301T>G p.Tyr101Asp Tyr84Asp Versailles lab. Feb 2012 odonto c.[301T>G];[=] ++
5 c.303C>A p.Tyr101* P Tyr84Ter Alonso et al. 2019 adult with unspecific signs (osteoporosis) c.[303C>A];[=] na
5 c.303_311del p.Asn102_Asn104del P Asn85_Asn87del

del Angel et al. 2020

del Angel et al. 2020

perinatal

adult

c.[303_311del];[1471G>A]

c.[303_311del];[=]

2.6 del Angel et al. 2020 26.3 del Angel et al. 2020 na
5 c.311A>G p.Asn104Ser P Asn87Ser Bhadada et al. 2020 Adult c.[311A>G];[=] ++
5 c.314C>A p.Ala105Asp Ala88Asp Communicated by Sue Krug
Soft Bones U.S. Oct. 2018
adult c.[314C>A];[=] 2.7 del Angel et al. 2020 40.4 del Angel et al. 2020 ++
5 c.317A>G p.Gln106Arg Gln89Arg Communicated by Dr M.G.
Benzrihen, Hospital Alejandro
Posedas, Argentina
childhood c.[317A>G];[=] ++
5 c.318G>C p.Gln106His LP Gln89His

Balasubramaniam et al. 2010

perinatal

c.[318G>C];[318G>C]

++
5 c.323C>T p.Pro108Leu P Pro91Leu Herasse et al. 2003 odonto c.[323C>T];[=] 1.9 Fauvert et al. 2009 24.0 Fauvert et al. 2009 ++
5 c.327C>A p.Asp109Glu Asp92Glu Bone Metabolism Unit,
Instituto Auxologico Italiano
IRCCS, Milano, Italy
adult c.[327C>A];[327C>A] ++
5 c.331G>A p.Ala111Thr P Ala94Thr

Goseki-Sone et al. 1998

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

Zankl et al. 2008



odonto

odonto

perinatal

perinatal

perinatal

c.[331G>A];[=]

c.[331G>A];[=]

c.[331G>A];[331G>A]

c.[331G>A];[1354G>A]

c.[331G>A];[c.400_401delinsCA]

2.0

3.4

Fauvert et al. 2009

del Angel et al. 2020

48.7

51.1

Fauvert et al. 2009

del Angel et al. 2020

++
5 c.332_335del p.Gly111fs Mornet et al. 2020 infantile c.[332_335del];[1471G>A] na
5 c.333del p.Gly112Alafs P Gly95Alafs Bai et al. 2016 perinatal c.[333del];[568_570del] na
5 c.334G>A p.Gly112Ser LP Gly95Ser

Witters et al. 2004

del Angel et al. 2020

Tenorio et al. 2017

del Angel et al. 2020

infantile

infantile

adult

odonto

c.[334G>A];[1171C>T]

c.[334G>A];[571G>A]

c.[334G>A];[=]

c.[334G>A];[=]

++
5 c.334G>C p.Gly112Arg P Gly95Arg Whyte et al. 2015 odonto. c.[334G>C];[=] ++
5 c.335_340dup p.Gly112_113dup P Gly95_96dup Wenkert et al. 2011 prenatal benign c.[335_340dup];[571G>A] na
5 c.340G>A p.Ala114Thr P Ala97Thr

Mumm et al. 2001

Whyte et al. 2015

Tenorio et al. 2017

del Angel et al. 2020

del Angel et al. 2020

infantile

childhood

childhood

adult

adult

c.[340G>A];[811A>C]

c.[340G>A];[=]

c.[340G>A];[=]

c.[340G>A];[c.407G>A]

c.[340G>A];[=]

3.0 del Angel et al. 2020 49.2 del Angel et al. 2020 ++
5 c.341C>G p.Ala114Gly P Ala97Gly Draguet et al. 2004 perinatal

c.[341C>G;348_349insACCGTC];[976G>C]

++
5 c.341C>T p.Ala114Val P Ala97Val Versailles lab march 2016 adult

c.[341C>T];[=]

5.2 del Angel et al. 2020 45.0 del Angel et al. 2020 ++
5 c.344C>T p.Thr115Ile P Thr98Ile Versailles lab Feb. 2019 odonto c.[344C>T];[407G>A] 11.4 del Angel et al. 2020 54.3 del Angel et al. 2020 ++
5 c.346G>T p.Ala116Ser P Ala99Ser Versailles lab Jul 2007 adult c.[346G>T];[1250A>G] ++
5 c.346G>A p.Ala116Thr P Ala99Thr

Hu et al. 2000

Lia-Baldini et al. 2001

Saglam et al. 2017

Saglam et al. 2017

Taillandier et al. 2015

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

adult

adult

odonto

childhood

childhood

adult

infantile

perinatal

c.[346G>A];[=]

c.[346G>A];[=]

c.[346G>A];[=]

c.[346G>A];[=]

c.[346G>A];[=]

c.[346G>A];[571G>A]

c.[346G>A];[571G>A]

c.[346G>A];[631A>G]

0.8

3.7

Lia-Baldini et al. 2001

del Angel et al. 2020

40.0

27.0

Lia-Baldini et al. 2001

del Angel et al. 2020

++
5 c.343_348dup p.Thr115_Ala116dup P


Thr98_Ala99dup

Draguet et al. 2004

Versailles lab March 2009

Tenorio et al. 2017

perinatal

odonto

childhood

c.[Ala116Gly+343_348dup];[976G>C]

c.[343_348dup];[=]

c.[343_348dup];[=]

na
5 c.350A>G p.Tyr117Cys P Tyr100Cys

Whyte et al. 2009

del Angel et al. 2020

childhood

adult


c.[350A>G];[400_401delinsCA]

c.[350A>G];[=]

+
5 c.352C>A p.Leu118Met P Leu101Met Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[352C>A];[352C>A] 50.0 del Angel et al. 2020 108 del Angel et al. 2020 ++
5 c.358G>A p.Gly120Arg P Gly103Arg Mornet et al. 1998 perinatal c.[358G>A];[648+1G>A] ++
5 c.359G>C p.Gly120Ala LP Gly103Ala Mao et al.2019 infantile c.[359G>C];[359G>C] ++
5 c.360_361del p.Val121Glufs Val104Glufs Vidmar et al. 2017 perinatal c.[360_361del];[46_49del] na
5 c.361G>A p.Val121Met Val104Met

Versailles lab dec. 2015

Lefever et al. 2018

childhood

adult

c.[361G>A];[=]

c.[361G>A];[=]

++
5 c.368C>A p.Ala123Asp P Ala106Asp Spentchian et al. 2006 perinatal c.[368C>A];[797_802del] +
5 c.379A>G p.Thr127Ala Thr110Ala Seefried et al. 2017 Adult c.[379A>G];[526G>A] ++
5 c.382G>A p.Val128Met P Val111Met

Mumm et al. 2002

Tenorio et al. 2017

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

perinatal

adult

childhood

childhood

infantile

childhood

c.[382G>A];[667C>T]

c.[382G>A];[=]

c.[382G>A];[382G>A]

c.[382G>A];[395C>T]

c.[382G>A];[1016G>A]

c.[382G>A];[395C>T]

60.6 del Angel et al. 2020 68.5 del Angel et al. 2020 +
5 c.388_389insG p.Val130Glyfs Val113Glyfs Riancho-Zarrabeitia et al. 2016
Tornero et al. 2020
asymtomatic* or very mild symptoms c.[388_389insG];[?] na
5 c.385G>A p.Gly129Arg P Gly112Arg Mornet et al. 1998 perinatal c.[385G>A];[1471G>A] ++
5 c.389_392del p.Val130Alafs Val113Alafs Spentchian et al. 2003 perinatal c.[389_392del];[931G>A] na
5 c.389del p.Val130Glufs P Val113Glufs Spentchian et al. 2003 perinatal c.[389del];[389del] na
5 c.392del p.Ser131Thrfs P Ser114Thrfs Mumm et al. 2002 perinat/infant c.[392del];[1042G>A] na
5 c.394G>A p.Ala132Thr P Ala115Thr

Versailles lab Jul 2006

del Angel et al. 2020

adult

odonto

c.[394G>A];[571G>A]

c.[394G>A];[407G>A]

++
5 c.395C>T p.Ala132Val P Ala115Val Watanabe et al. 2001 adult c.[395C>T];[?] 16.9 Watanabe et al. 2005 ++
5 c.400_401delinsCA p.Thr134His P Thr117His

Mumm et al. 2002

Daniel et al. 2018

del Angel et al. 2020

del Angel et al. 2020

perinatal

childhood

perinatal

perinatal

c.[400_401delinsCA];[984_986del]

c.[400_401delinsCA];[350A>G]

c.[400_401delinsCA];[400_401delinsCA]

c.[400_401delinsCA];[382G>A]

13.8 del Angel et al. 2020 81.7 del Angel et al. 2020 +
5 c.401C>A p.Thr134Asn P Thr117Asn Taillandier et al. 2000 perinatal c.[401C>A];[401C>A]

20.5

34.5

Taillandier et al. 2000

del Angel et al. 2020

129.2 del Angel et al. 2020 +
5 c.406C>T p.Arg136Cys P Arg119Cys

Versailles lab oct. 2003

Schmidt et al. 2017

odonto

adult

c.[406C>T];[407G>A]

c.[406C>T];[=]

5.0 del Angel et al. 2020 78.1 del Angel et al. 2020 ++
5 c.407G>A p.Arg136His P Arg119His

Taillandier et al. 1999

Whyte et al. 2015

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

Tenorio et al. 2017

del Angel et al. 2020

infantile

infantile

odonto

adult

childhood

adult

adult

adult

adult

c.[407G>A];[485G>T]

c.[407G>A];[212G>A]

c.[407G>A];[406C>T]

c.[407G>A];[512A>G]

c.[407G>A];[889T>G]

c.[407G>A];g.[(?_64307)_(64441_?)del]

c.[407G>A];[=]

c.[407G>A];[=]

c.[407G>A];[984_986del]

33.4

21.2

Zurutuza et al. 1999

del Angel et al. 2020

70.0

71.2

Fauvert et al. 2009

del Angel et al. 2020

++
5 c.407G>T p.Arg136Leu P Arg119Leu Yang et al. 2013 childhood c.[407G>T];[1166C>A] 35 Yang et al. 2013

62

Yang et al. 2013 ++
5 c.407G>C p.Arg136Pro P Arg119Pro Cui et al. 2012 infantile c.[18del];[407G>C] ++
5 c.412_413dupC p.Arg138Profs Arg121Profs Xu et al. 2018 childhood c.[412_413dupC];[=] na
5 c.413G>C p.Arg138Pro Arg121Pro Castells et al. 2018 perinatal c.[413G>C];[473-2G>C]? 3.2 del Angel et al. 2020 44.2 del Angel et al. 2020 +
5 c.416G>A p.Cys139Tyr Cys122Tyr Collagen Diagnosis Laboratory,
University of Washington, USA,
Febr. 2018
childhood c.[416G>A];[=] 9.5 del Angel et al. 2020 64.8 del Angel et al. 2020 ++
5 c.422C>A p.Thr141Asn P Thr124Asn Whyte et al. 2015 childhood c.[422C>A];[629A>G] ++
5 c.422C>T p.Thr141Ile P Thr124Ile

Versailles lab Jul 2008

del Angel et al. 2020

infantile

infantile

c.[422C>T];[920C>T]

c.[422C>T];[422C>T]

61.5 del Angel et al. 2020 120 del Angel et al. 2020 ++
5 c.427del p.Gln143Argfs P Gln126Argfs Whyte et al. 2015 childhood c.[427del];[1444C>A] na
5 c.431G>A p.Gly144Glu P Gly127Glu Versailles lab April 2018 adult c.[431G>A];[=] 82.3 del Angel et al. 2020 94.9 del Angel et al. 2020 ++
5 c.436G>A p.Glu146Lys VUS Glu129Lys Nielson et al. 2012

Alonso et al. 2019
asymptomatic*, low BMD

adult with unspecific signs (osteoporosis)
c.[436G>A];[=] 72.7 del Angel et al. 2020 96.1 del Angel et al. 2020 ++
5 c.442A>G p.Thr148Ala P Thr131Ala Michigami et al. 2005 perinatal c.[442A>G];[?] ++
5 c.443C>T p.Thr148Ile P Thr131Ile

Spentchian et al. 2003

del Angel et al. 2020

Tenorio et al. 2017

infantile

childhood

adult

c.[443C>T];[484G>A]

c.[443C>T];[443C>T]

c.[443C>T];[=]

24.9 del Angel et al. 2020 91.6 del Angel et al. 2020 ++
5 c.454C>T p.Arg152Cys P Arg135Cys

Versailles lab Nov. 2009

Martins et al. 2013

adult

odonto

c.[454C>T];[550C>T]

c.[454C>T];[1318_1320del]

49.9 del Angel et al. 2020 75.1 del Angel et al. 2020 +
5 c.457T>C p.Trp153Arg P Trp136Arg Wenkert et al. 2011 prenatal benign c.[1183A>G];[457T>C] ++
5 c.461C>T p.Ala154Val Ala137Val Yu et al. 2019 perinatal c.[461C>T];[406C>T] ++
5 c.466G>T p.Asp156Tyr Asp139Tyr Taillandier et al. 2017 Adult c.[466G>T];=] +
IVS5 c.472+1G>A P Liu et al. 2010 odonto c.[472+1G>A];[1120G>A] na
IVS5 c.473-2A>G P Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[473-2A>G];[?] na
6 c.480del P

Versailles lab. Jan. 2008


perinatal


c.[480del];[667C>T]

na
6 c.484G>A p.Gly162Ser P Gly145Ser

Spentchian et al. 2003

del Angel et al. 2020

del Angel et al. 2020

infantile

perinatal

adult

c.[484G>A];[443C>T]

c.[484G>A];[407G>A]

c.[484G>A];[=]

19.3 del Angel et al. 2020 75.1 del Angel et al. 2020 ++
6 c.485G>T p.Gly162Val P Gly145Val Taillandier et al. 1999 infantile c.[407G>A];[485G>T] 1.3 Zurutuza et al. 1999 ++
6 c.491T>G p.Val164Gly Val147Gly Versailles lab March 2009 infantile c.[491T>G];[811A>C] ++
6 c.494C>T p.Thr165Ile P Thr148Ile Versailles lab April 2018 adult c.[494C>T];[=] 5.6 del Angel et al. 2020 65.6 del Angel et al. 2020 ++
6 c.497C>T p.Thr166Ile P Thr149Ile Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[497C>T];[=] ++
6 c.500C>T p.Thr167Met P Thr150Met

Versailles lab Oct. 2003
Braunstein et al. 2015

Whyte et al. 2015

infantile

adult

childhood severe

c.[500C>T];[571G>A]

c.[500C>T];[=]

c.[500C>T];[407G>A]

3.5 del Angel et al. 2020 45.0 del Angel et al. 2020 +
6 c.508A>G p.Asn170Asp P Asn153Asp Mornet et al. 1998 perinatal c.[508A>G];[508A>G] 0 Ito et al. 2002 +
6 c.511C>T p.His171Tyr P His154Tyr Taillandier et al. 1999 infantile c.[511C>T];[571G>A] 2.1 Zurutuza et al. 1999 ++
6 c.512A>G p.His171Arg P His154Arg

Bükmann Larsen et al. 2018

Tenorio et al. 2017

del Angel et al. 2020

adult

adult

infantile

c.[512A>G];[571G>A]

c.[512A>G];[=]

c.[512A>G];[542C>T]

4.3 del Angel et al. 2020 37.1 del Angel et al. 2020 ++
6 c.518C>T p.Thr173Ile P Thr156Ile C.V. Lago, Military Police
Hospital M.G., Belo
Horizonte, Brazil, July 2017
childhood c.[518C>T];[=] 5.7 del Angel et al. 2020 23.8 del Angel et al. 2020 ++
6 c.522del p.Ser175Alafs Ser158Alafs Clinvar (Counsyl) infantile not provided na
6 c.526G>A p.Ala176Thr P Ala159Thr

Taillandier et al. 2000

Stevenson et al. 2008

Reib

Reibel et al 2009

Lawrence et al. 2017

Mori et al. 2016

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

childhood

prenatal benign

odonto

childhood

adult

adult

childhood

infantile

childhood

adult

odonto

c.[526G>A];[738G>T]

c.[526G>A];[814C>T]

c.[526G>A];[571G>A]

c.[526G>A];[648+1G>A]

c.[526G>A];[1171C>T]

c.[526G>A];[648+1G>A]

c.[526G>A];[881A>C]

c.[526G>A];[891C>A]

c.[526G>A];[997+2T]

c.[526G>A];[=]

c.[526G>A];[=]

45.4

67.6

Taillandier et al. 2000

del Angel et al. 2020

58.0

78.4

Fauvert et al. 2009

del Angel et al. 2020

++
6 c.529G>A p.Ala177Thr P Ala160Thr Goseki-Sone et al. 1998 adult c.[529G>A];[979T>C]

83.8

81.7

Orimo et al. 2001

del Angel et al. 2020

99.1 del Angel et al. 2020 +
6 c.532T>C p.Tyr178His P Tyr161His Ikenoue et al. 2017 perinatal c.[532T>C];[1559del] 0 Ikenoue et al. 2017 ++
6 c.535G>A p.Ala179Thr P Ala162Thr

Weiss et al. 1988

perinatal

c.[535G>A]:[535G>A]

18

9.2

Shibata et al.1998

del Angel et al. 2020

64.0 del Angel et al. 2020 ++
6 c.538C>A p.His180Asn His163Asn Versailles lab March 2016

Lefever et al. 2018
adult c.[538C>A];[=] ++
6 c.539A>G p.His180Arg His163Arg Versailles lab Dec. 2018 adult c.[539A>G];[=] 11.5 del Angel et al. 2020 92.7 del Angel et al. 2020 ++
6 c.542C>T p.Ser181Leu P Ser164Leu

Lia-Baldini et al. 2001

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

fdel Angel et al. 2020

del Angel et al. 2020

Tenorio et al. 2017

Riancho-Zarrabeitia et al. 2016

Martos-Moreno et al. 2017

infantile

perinatal

odonto

infantile

infantile

childhood

adult

adult

infantile

c.[542C>T];del(ex12)

c.[542C>T];[1250A>G]

c.[542C>T];[1282C>T]

c.[542C>T];[542C>T]

c.[542C>T];[853_854insdel]

c.[542C>T];[920C>T]

c.[542C>T];[=]

c.[542C>T];[=]

c.[542C>T];[644T>C]

1.3

55.3

Lia-Baldini et al. 2001

del Angel et al. 2020

54.4

89.4

del Angel et al. 2020

Lia-Baldini et al. 2001

++
6 c.544del p.Ala182Leufs P Ala165Leufs Taillandier et al. 1999 perinatal c.[544del];[746G>T] na
6 c.547G>C p.Asp183His P Asp166His Versailles lab Nov 2008 infantile c.[547G>C];[811A>C] +
6 c.550C>T p.Arg184Trp P Arg167Trp

Mornet et al. 1998

Michigami et al.2020

del Angel et al. 2020

del Angel et al. 2020

perinatal

odonto

odonto

adult

c.[550C>T];[809G>A]

c.[550C>T];[=]

c.[550C>T];[=]

c.[550C>T];[454C>T]

0.6

0

3.1

Lia-Baldini et al. 2001

Michigami et al.2020

del Angel et al. 2020

36.7

50

44.1

Lia-Baldini et al. 2001

Michigami et al.2020

del Angel et al. 2020

++
6 c.551G>A p.Arg184Gln P Arg167Gln

Versailles lab. Nov. 2013
del Angel et al. 2020

Mornet et al. 2020

infantile

adult

c.[551G>A];[203C>T]

c.[551G>A];[=]

3.8 del Angel et al. 2020 44.4 del Angel et al. 2020 ++
6 c.558G>A p.Trp186* Trp169*

Garcia-Fontana et al. 2019

Mornet et al. 2020

adult

adult

c.[558G>A];[=]

c.[558G>A];[571G>A]

na
6 c.562T>C p.Ser188Pro P Ser171Pro Oyachi et al. 2018 perinatal c.[562T>C];[1559del] 2.1 del Angel et al. 2020 63.6 ddel Angel et al. 2020 ++
6 c.565G>A p.Asp189Asn Asp172Asn communicated by A. O'Brien,
Sick Kids Hospital, Toronto,
Canada, April 2018
Adult c.[565G>A];[=] 7.9 del Angel et al. 2020 48.3 del Angel et al. 2020 ++
6 c.565_575delinsAG p.Asp189_Met192delinsArg Asp172_Met175delinsArg Dr I. RAU , Institüt für
Humangenetik, Hamburg,
Germany, Jan 2019
Adult c.[565_575delinsAG];[=] na
6 c.567C>A p.Asp189Glu P Asp172Glu Spentchian et al. 2003 perinatal c.[567C>A];[567C>A] ++
6 c.568_570del p.Asn190del P Asn173del Michigami et al. 2005 perinatal c.[568_570del];[1559del] na
6 c.571G>A p.Glu191Lys P Glu174Lys

Henthorn et al. 1992

Hofmann et al.2014

Hofmann et al.2014

Mao et al.2019

Mao et al.2019

Versailles lab Jul 2010

Tenorio et al. 2017

Reibel et al. 2009

Lefever et al.2018

del Angel et al. 2020

del Angel et al. 2020

Mornet et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020


infantile

childhood

infantile

childhood

childhood

adult

infantile

infantile

childhood

adult

prenatal benign

infantile

infantile

childhood

childhood, adult, odonto

c.[571G>A];[1133A>T]

c.[571G>A];[1001G>A]

c.[571G>A];[1001G>A]

c.[571G>A];[203C>T]

c.[571G>A];[212G>A]

c.[571G>A];[41T>C

c.[571G>A];[1133A>G]

c.[571G>A];[550C>T]

c.[571G>A];[1172G>A]

c.[571G>A];[1015G>C]

c.[571G>A];[1015G>C]

c.[571G>A];[1042G>A]

c.[571G>A];[1171C>T]

c.[571G>A];[1175G>C]

c.[571G>A];[=]

88.0


56.0


21.4

Zurutuza et al. 1999

Fauvert et al. 2009

del Angel et al. 2020

79.5


58.7




Fauvert et al. 2009

del Angel et al. 2020

++
6 c.572A>G p.Glu191Gly Glu174Gly

Goseki-Sone et al. 1998

Michigami et al.2020

Michigami et al.2020

odonto

odonto

perinatal benign

c.[572A>G];[1559del]

c.[572A>G];[1559del]

c.[572A>G];[1559del]

++
6 c.575T>C p.Met192Thr P Met175Thr


Versailles lab Jul 2007

Alonso et al. 2019

A.Rosen, Emory University,
Atlanta GA, USA. Jan 2020

infantile

adult with unspecific signs (osteoporosis)

childhood (mild form)

c.[575T>C];[931G>A]

c.[575T>C];[=]

c.[575T>C];[=]

57.6 del Angel et al. 2020 1.0 del Angel et al. 2020 ++
6 c.577C>G p.Pro193Ala P Pro176Ala Mumm et al. 2002 adult c.[340G>A];[577C>G] +
6 c.599G>A p.Gly200Asp P Gly183Asp Taillandier et al. 2015 adult c.[599G>A];[=] ++
6 c.601T>C p.Cys201Arg Cys184Arg Xu et al. 2018 adult c.[601T>C];[=] ++
6 c.602G>A p.Cys201Tyr P Cys184Tyr Taillandier et al. 1999 perinatal c.[-195C>T];[602G>A] 0 Satou et al. 2012 ++
6 c.609C>G p.Asp203Glu P Asp186Glu Versailles lab oct. 2004 perinatal c.[609C>G];[609C>G] 3.7 del Angel et al. 2020 59.1 del Angel et al. 2020 ++
6 c.614C>T p.Ala205Val Ala188Val Versailles lab aug. 2013 asymptomatic* c.[614C>T];[?] +
6 c.620A>C p.Gln207Pro P Gln190Pro Henthorn et al. 1992 perinatal c.[212G>C];[620A>C] ++
6 c.622C>T p.Leu208Phe Leu191Phe Versailles lab april 2009 perinatal c.[622C>T];[622C>T] ++
6 c.625A>T p.Met209Leu VUS Met192Leu Schmidt et al. 2019 adult c.[625A>T];[746G>T] +
6 c.629A>G p.His210Arg P His193Phe Whyte et al. 2015 childhood c.[422C>A];[629A>G] 20.2 del Angel et al. 2020 78.8 del Angel et al. 2020 +
6 c.630_637dup p.Arg213Ilefs Arg196Ilefs Versailles lab June 2011 perinatal c.[630_637dup];[792G>A] na
6 c.631A>G p.Asn211Asp P Asn194Asp Taillandier et al. 2001 infantile c.[346G>A];[631A>G] ++
6 c.634A>T p.Ile212Phe P Ile195Phe Souka et al. 2002 perinatal c.[634A>T];[1062G>C] +
6 c.643A>G p.Ile215Val Ile198Val adult c.[643A>G];[=] ++
6 c.644T>C p.Ile215Thr Ile198Thr Versailles lab. march 2011 infantile c.[542C>T];[644T>C] ++
IVS6 c.648+1G>T P Brun-Heath et al. 2005 perinatal c.[648+1G>T];[811A>C] na
IVS6 c.648+1G>A P

Mornet et al. 1998

perinatal

c.[358G>A];[648+1G>A]

na
IVS6 c.648+2dup

Versailles lab jan 2013

Mentrup et al.2016

perinatal c.[648+2dup];[1196C>T] na
IVS6 c.649-3_649-1delinsAA Versailles lab Jul 2006 perinatal c.[649-3_649-1delinsAA];[649-3_649-1delinsAA] na
7 c.650delinsCTAA p.217delValinsAlaLys 200delValinsAlaLys Chang et al. 2011 perinatal c.[650delinsCTAA];[984_986del] na
7 c.653T>C p.Ile218Thr P Ile201Thr

Utsch et al., 2009

perinatal c.[653T>C];[1171C>T] 3.7 Utsch et al., 2009 ++
7 c.655A>G p.Met219Val P Met202Val Yang et al. 2013 odonto c.[655A>G];[331G>A]

75

42.4

Yang et al. 2013

del Angel et al. 2020

80

86.5

Yang et al. 2013

del Angel et al. 2020

+
7 c.657G>T p.Met219Ile Met202Ile Versailles lab, Jan 2019 adult c.[657G>T];[=] 30.1 ddel Angel et al. 2020 77.0 del Angel et al. 2020 +
7 c.658G>A p.Gly220Arg P Gly203Arg Versailles lab Dec 2011 perinatal c.[658G>A];[658G>A] ++
7 c.659G>T p.Gly220Val Gly203Val Taillandier et al. 2001 odonto c.[571G>A];[659G>T] ++
7 c.659G>C p.Gly220Ala P Gly203Ala

Spentchian et al. 2006

del Angel et al. 2020

perinatal

infantile

perinatal

c.[659G>C];[659G>C]

c.[659G>C];[659G>C]

c.[659G>C];[668G>A]

23.1 del Angel et al. 2020 66.7 del Angel et al. 2020 ++
7 c.661G>C p.Gly221Arg P Gly204Arg

Versailles lab March 2009

del Angel et al. 2020

perinatal

perinatal

c.[661G>C];[?]

c.[661G>C];[920C>T]

4.2 del Angel et al. 2020 65.2 del Angel et al. 2020 ++
7 c.662dup p.Gly222Trpfs Gly205Trpfs Mornet et al. 2020 perinatal c.[130C>T];[662dup] na
7 c.662del p.Gly221Valfs P Gly204Valfs Spentchian et al. 2003 perinatal c.[662del];[815G>T] na
7 c.662G>T p.Gly221Val P Gly204Val Versailles lab oct. 2004 perinatal c.[662G>T];[1064T>C] ++
7 c.667C>T p.Arg223Trp P Arg206Trp Mornet et al. 1998 perinatal c.[667C>T];[?] 2.8 Lia-Baldini et al. 2001 51.9 Lia-Baldini et al. 2001 ++
7 c.668G>A p.Arg223Gln P Arg206Gln

Mumm et al. 2002

Mumm et al. 2002

del Angel et al. 2020

perinatal

infantile

adult

c.[668G>A];[0]

c.[668G>A];[881A>C]

c.[668G>A];[=]

2.9

5.0

Zhu et al. 2012

del Angel et al. 2020

37.5 del Angel et al. 2020 ++
7 c.670A>G p.Lys224Glu P Lys207Glu Mochizuki et al. 2000 infantile c.[670A>G];[1276G>T] 43 Michigami et al. 2005 ++
7 c.677T>C p.Met226Thr P Met209Thr

Baumgartner-Sigl et al. 2007

Mornet et al. 2020

infantile

adult

c.[677T>C];[1112C>T]

c.[677T>C];[=]

++
7 c.704A>T p.Glu235Val Glu218Val Michigami et al.2020 odonto c.[704A>T];[1559del]
7 c.704A>G p.Glu235Gly P Glu218Gly Taillandier et al. 2001 adult c.[704A>G];[1195G>T]

3.6

3.3

Mornet et al. 2001

del Angel et al. 2020

62.4 del Angel et al. 2020 ++
7 c.708T>G p.Tyr236* p Tyr219* Vogt et al. 2020 childhood c.[708T>G];[350A>G] na
7 c.715G>T p.Asp239Tyr Asp222Tyr Saraff et al. 2016 asymptomatic* c.[715G>T];[715G>T] +
7 c.734C>T p.Thr245Met Thr228Met Versailles lab May 2016 prenatal benign? (not confirmed) c.[734C>T];[?] 59.3 del Angel et al. 2020 88.7 del Angel et al. 2020 ++
7 c.738G>T p.Arg246Ser Arg229Ser

Taillandier et al. 2000

childhood

c.[526G>A];[738G>T]

4.4

4.5

Taillandier et al. 2000

del Angel et al. 2020

52.0 del Angel et al. 2020 ++
7 c.746G>T p.Gly249Val P Gly232Val Fedde et al. 1996 perinatal c.[746G>T];[=]

34.5

36.3

Lia-Baldini et al. 2001

del Angel et al. 2020

70.5

80.6

Lia-Baldini et al. 2001

del Angel et al. 2020

+
7 c.791A>G p.Lys264Arg P Lys247Arg

Brun-Heath et al. 2007

perinatal

c.[791A>G];[1133A>T]

+
7 c.792G>A p.Lys264Lys Lys247Lys

Versailles lab june 2011

perinatal

c.[792G>A];[630_637dup]

na (splice)
IVS7 c.793-14_33del Mentrup et al. 2016 infantile c.[793-14_33del];[793-14_33del] 0 Mentrup et al. 2016 50 Mentrup et al. 2016 na
8 c.797_802del p.Ser266_His267del P Ser249_His250del Spentchian et al. 2006 perinatal c.[368C>A];[797_802del] na
8 c.799_804del p.His267_Phe268del P p.His250_Phe251del Saglam et al. 2017 perinatal c.[799_804del];[799_804del] na
8 c.809G>A p.Trp270* P Trp253*

Mornet et al. 1998

del Angel et al. 2020

del Angel et al. 2020

perinatal

perinatal

adult

c.[809G>A];[550C>T]

c.[809G>A];[1228T>C]

c.[809G>A];[=]

1.2 Zurutuza et al. 1999 na
8 c.814C>T p.Arg272Cys P Arg255Cys

Spentchian et al. 2006

perinatal

c.[814C>T];[400_401delinsCA]

6.7 del Angel et al. 2020 79.6 del Angel et al. 2020 ++
8 c.814del p.Arg272Alafs Arg255Alafs

Versailles lab June 2011
del Angel et al. 2020

del Angel et al. 2020

perinatal

adult

c.[814del];[1142A>G]

c.[814del];[=]

na
8 c.815G>T p.Arg272Leu P Arg255Leu Spentchian et al. 2003 perinatal c.[815G>T];[662del] 33.7 del Angel et al. 2020 55.4 del Angel et al. 2020 ++
8 c.815G>A p.Arg272His P Arg255His

Brun-Heath et al. 2005

del Angel et al. 2020

Mornet et al. 2020

infantile

odonto

adult

c.[815G>A];[815G>A]

c.[815G>A];[=]

c.[815G>A];[=]

6.8

43.7

Brun-Heath et al. 2005

del Angel et al. 2020

89.9 del Angel et al. 2020 ++
8 c.824T>C p.Leu275Pro P Leu258Pro Orimo et al. 2002 childhood c.[824T>C];[529G>A] 3.3 Orimo et al. 2001 ++
8 c.841del p.His281Thrfs His264Thrfs Clinvar (Counsyl) infantile not provided na
8 c.850_853dupGACT p.Tyr285* Tyr268* Michigami et al. 2005 perinatal c.[850_853dupGACT];[1559del] na
IVS8 c.862+5G>A P Taillandier et al. 1999 infantile c.[862+5G>A];[862+5G>A] na
9 c.865C>T p.Leu289Phe P Leu272Phe Sugimoto et al. 1998 infantile c.[865C>T];[1559del] 50 Sugimoto et al. 1998 ++
9 c.868_869del p.Phe290fs LP Phe273fs Versailles lab Sept 2019 adult c.[868_869del];[=] na
9 c.871G>A p.Glu291Lys P Glu274Lys Mornet et al. 1998 infantile c.[571G>A];[871G>A]

8.3

3.9

Zurutuza et al. 1999

del Angel et al. 2020

79.2 del Angel et al. 2020 ++
9 c.871G>T p.Glu291* P Glu274Ter

Taillandier et al. 2000

Mornet et al. 2020

perinatal

perinatal

c.[871G>T];[331G>A]

c.[871G>T];[385G>A]

3.2 del Angel et al. 2020 61.0 del Angel et al. 2020 na
9 c.871G>C p.Glu291Gln Glu274Gln Versailles lab Jun 2010 perinatal c.[871G>C];[871G>C] 41.5 del Angel et al. 2020 92.0 del Angel et al. 2020 ++
9 c.874C>A p.Pro292Thr P Pro275Thr Brun-Heath et al. 2005 infantile c.[98C>T];[874C>A]

4.0

63.5

Brun-Heath et al. 2005

del Angel et al. 2020

89.2 del Angel et al. 2020 ++
9 c.874C>T p.Pro292Ser P Pro275Ser Tenorio et al. 2017 c.[815G>T];[874C>T] ++
9 c.875_881delinsT p.Gly293_Asp294del P Gly276_Asp277del

Belachew et al. 2013

Prevention Genetics

perinatal

childhood severe

c.[875_881delinsT];[1559del]

c.[875_881delinsT];[=]

na
9 c.876_881del p.Gly293_Asp294del P Gly276_Asp277del Spentchian et al. 2003 perinatal c.[876_881del];[963del] na
9 c.880G>T p.Asp294Tyr P Asp277Tyr Taillandier et al. 2001 infantile c.[880G>T];[526G>A] ++
9 c.881A>C p.Asp294Ala P Asp277Ala

Henthorn et al. 1992

Mumm et al. 2002

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

infantile

infantile

infantile

adult

infantile

perinatal

c.[881A>C];[211C>T]

c.[881A>C];[668G>A]

c.[881A>C];[979T>C]

c.[881A>C];[571G>A]

c.[881A>C];[547G>C]

c.[881A>C];[1553_1559del]

35

8.9

Fukushi-Irié et al. 2000

del Angel et al. 2020

89.2

89.2

del Angel et al. 2020 ++
9 c.883A>G p.Met295Val P Met278Val Mornet et al. 2001 childhood c.[883A>G];[571G>A] +
9 c.884T>C p.Met295Thr P Met278Thr

Brun-Heath et al. 2005

del Angel et al. 2020

perinatal

adult

c.[884T>C;[667C>T]

c.[884T>C];[400_401delinsCA]

8.5

22.7

Brun-Heath et al. 2005

del Angel et al. 2020

95.3 del Angel et al. 2020 +
9 c.885G>A p.Met295Ile P Met278Ile Michigami et al. 2005 perinatal c.[885G>A];[1559del] +
9 c.886C>T p.Gln296* Gln279* Plendl et al. 2011 adult c.[886C>T];[?] na
9 c.889T>G p.Tyr297Asp P Tyr280Asp Brun-Heath et al. 2005 childhood c.[407G>A];[889T>G] 1.3 Brun-Heath et al. 2005 ++
9 c.889T>C p.Tyr297His P Tyr280His Bertola et al. 2009 perinatal c.[648+1G>A];[889T>C] ++
9 c.889T>A p.Tyr297Asn Tyr280Asn Research center for medical
genetics, Moscow, Oct. 2015
childhood c.[889T>A];[?] ++
9 c.891C>G p.Tyr297* P Tyr280* Versailles lab March 2020 adult c.[891C>G];[=] na
9 c.891C>A p.Tyr297* P Tyr280* Balasubramaniam et al. 2010 infantile c.[891C>A];[1471G>A] 2.8 del Angel et al. 2020 62.3 del Angel et al. 2020 na
9 c.892G>A p.Glu298Lys P Glu281Lys Orimo et al. 1994 infantile c.[892G>A];[1559del] 23.7 del Angel et al. 2020 90.7 del Angel et al. 2020 ++
9 c.896T>C p.Leu299Pro P Leu282Pro

Versailles lab oct. 2003

del Angel et al. 2020

infantile

odonto

c.[896T>C];[896T>C]

c.[896T>C];[=]

9.7

38.2

Michigami et al. 2005

del Angel et al. 2020

96.7 del Angel et al. 2020 ++
9 c.901A>T p.Arg301Trp LP Arg284Trp Alonso et al. 2019 adult with unspecific signs (osteoporosis) c.[901A>T];[=] ++
9 c.902del p.Asn302Thrfs p.Asn285Thrfs Research center for medical
genetics, Moscow, Nov. 2016
childhood c.[902del];[?] na
9 c.917A>T p.Asp306Val P Asp289Val Taillandier et al. 1999 infantile c.[917A>T];[917A>T]

0

3.4

Ishida et al. 2003

del Angel et al. 2020

57.1 del Angel et al. 2020 ++
9 c.919C>T p.Pro307Ser P Pro290Val Versailles lab oct. 2004 infantile c.[919C>T];[1400T>C] ++
9 c.920C>T p.Pro307Leu LP Pro290Leu

Versailles lab Jul. 2006

Alonso et al. 2019

del Angel et al. 2020

childhood

adult with unspecific signs (osteoporosis)

infantile

c.[920C>T];[542C>T]

c.[920C>T];[=]

c.[920C>T];[=]

5.3 del Angel et al. 2020 89.9 del Angel et al. 2020 ++
9 c.928_929del p.Ser310Argfs P Ser293Argfs Brun-Heath et al. 2005 perinatal c.[928_929del];[1231A>G] na
9 c.931G>A p.Glu311Lys P Glu294Lys Spentchian et al. 2003 perinatal c.[931G>A];[389_392del] 3.9 del Angel et al. 2020 77.9 del Angel et al. 2020 ++
9 c.952C>T p.Gln318* Gln301* Versailles lab Dec 2011 perinatal c.[952C>T];[1216G>A] na
9 c.963del p.Lys322Argfs P Lys305Argfs Spentchian et al. 2003 perinatal c.[876_881del];[963del] na
9 c.968A>T p.Asn323Ile Asn306Ile City Hospital #40, St Petersburg,
Russia
childhood c.[968A>T];[?] ++
9 c.969C>G p.Asn323Lys Asn306Lys Versailles lab oct. 2009 childhood c.[648+1G>A];[969C>G] ++
9 c.976G>C p.Gly326Arg P Gly309Arg Litmanovitz et al. 2002 perinatal c.[976G>C];[871G>A]] ++
9 c.977G>T p.Gly326Val P Gly309Val Versailles lab Jul 2008 perinatal c.[977G>T];[977G>T] ++
9 c.980T>G p.Phe327Cys P Phe310Cys

Mornet et al. 2001

McKiernan et al.2017

perinatal

asymptomatic*

c.[401C>A];[980T>G]

c.[980T>G];[=]

++
9 c.979_980delinsGG p.Phe327Gly P Phe310Gly Taillandier et al. 2001 adult c.[571G>A];[979_980delinsGG] ++
9 c.979T>C p.Phe327Leu P Phe310Leu

Ozono et al. 1996

Mao et al.2019

Michigami et al.2020

infantile

odonto

odonto

c.[979T>C];[1366G>A]

c.[979T>C];[1017dupG]

c.[979T>C];[1559del]

72

97.5

Cai et al. 1998

del Angel et al. 2020

1.24 del Angel et al. 2020 ++
9 c.982T>C p.Phe328Leu P Phe311Leu Michigami et al. 2005 perinatal benign c.[299C>T];[982T>C] 10 Michigami et al. 2005 ++
9 c.984_986del p.Phe328del P Phe311del

Orimo et al. 1997

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

infantile

perinatal

childhood

perinatal

adult

childhood

c.[984_986del];[1559del]

c.[984_986del];[1460C>T]

c.[984_986del];[571G>A]

c.[984_986del];[648+5G>C]

c.[984_986del];[=]

c.[984_986del];[=]

10

4.5

Michigami et al. 2005

del Angel et al. 2020

70.4 del Angel et al. 2020 na
IVS9 c.997+1G>T P Liu et al. 2010 odonto c.[997+1G>T];[1162T>C] na
IVS9 c.997+2T>A P Taillandier et al. 2000 perinatal c.[997+2T>A];[1466G>C] na
IVS9 c.997+2T>G P Brun-Heath et al. 2005 perinatal c.[997+2T>G];[997+2T>G] na
IVS9 c.997+3A>C P Mornet et al. 1998 perinatal c.[997+3A>C];[997+3A>C] na
IVS9 c.997+3A>G P Wenkert et al. 2011 prenatal benign c.[997+3A>G];[1181_1182del] na
IVS9 c.998-2A>G Clinvar (Counsyl) infantile not provided na
IVS9 c.998-1G>T P Taillandier et al. 2001 perinatal c.[571G>A];[998-1G>T] na
10 c.1000G>C p.Gly334Arg P Gly317Arg Fauvert et al. 2009 odonto c.[1000G>C];[=] 5.0 Fauvert et al. 2009 39.0 Fauvert et al. 2009 ++
10 c.1001G>A p.Gly334Asp P Gly317Asp


Greenberg et al. 1993

Hofmann et al.2014

del Angel et al. 2020

del Angel et al. 2020

Rolvien et al. 2019

perinatal

childhood

perinatal

odonto

infantile

c.[1001G>A];[1001G>A]

c.[1001G>A];[571G>A]

c.[1001G>A];[1444dup]

c.[1001G>A];[=]

c.[1001G>A];[=]

0

6.5

Fukushi et al. 1998

del Angel et al. 2020

40.0

28.3

Fauvert et al. 2009

del Angel et al. 2020

++
10 c.1004G>C p.Arg335Thr Arg318Thr Institute of Human Genetics,
UK Hamburg-Eppendorf, Germany
adult c.[1004G>C];[=] 6.0 del Angel et al. 2020 47.5 del Angel et al. 2020 ++
10 c.1010A>G p.Asp337Gly P Asp320Gly Whyte et al. 2015 childhood c.[571G>A];[1010A>G] 4.1 del Angel et al. 2020 32.1 del Angel et al. 2020 ++
10 c.1015G>A p.Gly339Arg Gly322Arg Mumm et al. 2002 perinatal c.[526G>A];[1015G>A]

1.1

3.7

Fauvert et al. 2009

del Angel et al. 2020

33.0

45.8

Fauvert et al. 2009

del Angel et al. 2020

++
10 c.1015G>C p.Gly339Arg P Gly322Arg

Schalin-Jantti et al. 2010

del Angel et al. 2020

adult

odonto


[1015G>C];[571G>A]

c.[1015G>C];[=]

++
10 c.1016G>A p.Gly339Glu P Gly322Glu Versailles lab oct. 2004 infantile c.[382G>A];[1016G>A] ++
10 c.1017dup p.His340Alafs P p.His323Alafs Mao et al.2019 odonto c.[979T>C];[1017dup] na
10 c.1022A>G p.His341Arg P His324Arg Versailles lab Dec. 2018 prenatal benign (likely) c.[1022A>G];[?] 4.4 del Angel et al. 2020 37.8 del Angel et al. 2020 ++
10 c.1039C>T p.Gln347* P Gln330* Park et al. 2016 infantile c.[334G>A];[1039C>T] na
10 c.1042G>A p.Ala348Thr P Ala331Thr Taillandier et al. 2000 infantile c.[571G>A];[1042G>A] 33.2 Taillandier et al. 2000 ++
10 c.1044_1055del p.Leu349_Ala352del P Leu332_Ala335del Spentchian et al. 2006 perinatal c.[1044_1055del];[1471G>A] na
10 c.1062G>C p.Glu354Asp P Glu337Asp Souka et al. 2002 perinatal c.[634A>T];[1062G>C] ++
10 c.1064T>C p.Met355Thr P Met338Thr Versailles lab oct. 2004 perinatal c.[662G>T];[1064T>C] ++
10 c.1065G>A p.Met355Ile P Met338Ile Versailles lab. Jan. 2008 infantile c.[1065G>A];[1171C>T] ++
10 c.1068C>G p.Asp356Glu VUS Asp339Glu McKiernan et al.2017 asymptomatic* c.[1068C>G];[=]
10 c.1068C>A p.Asp356Glu VUS Asp339Glu Versailles lab Apr 2011 perinatal c.[668G>A];[1068C>A] ++
10 c.1070G>T p.Arg357Leu Arg340Leu Nielson et al. 2012 asymptomatic*, low BMD

c.[1070G>T];[?]

+
10 c.1072G>A p.Ala358Thr Ala 341Thr Research center for medical
genetics, Moscow, Nov. 2015
adult c.[1072G>A];[?] ++
10 c.1077C>G p.Ile359Met P Ile342Met Whyte et al. 2012 infantile c.[1077C>G];[1133A>T] ++
10 c.1078_1081dup p.Gln361Argfs P Gln344Argfs Versailles lab, May 2020 adult c.[1078_1081dup];[1417G>A] na
10 c.1083_1084dup p.Ser364Argfs Ser347Argfs Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[1083_1084dup];[?] na
10 c.1088_1091dup p.Ser364Argfs P Ser347Argfs

Clinvar (Counsyl)

infantile

not provided

na
10 c.1097C>A p.Thr366Asn Thr349Asn Versailles lab march 2016 asymtomatic* or very mild symptoms c.[1097C>A];[?] ++
10 c.1101_1103del p.Ser368del P Ser351del Versailles lab oct. 2004 perinatal c.[1101_1103del];[1166C>T] na
10 c.1112C>T p.Thr371Ile P Thr354Ile Baumgartner-Sigl et al. 2007 infantile c.[677T>C];[1112C>T] ++
10 c.1120G>A p.Val374Met P Val357Met Versailles lab oct. 2004

Alonso et al. 2019
adult

adult with unspecific signs (osteoporosis)
c.[892G>A];[1120G>A]


c.[1120G>A];[=]

57.6

98.9

Zhu et al. 2012

del Angel et al. 2020

1.12 del Angel et al. 2020 +
10 c.1130C>T p.Ala377Val P Ala360Val


Mornet et al. 2001

del Angel et al. 2020

perinatal

Odonto

c.[1130C>T];[1130C>T]

c.[1130C>T];[=]

0

2.3

Michigami et al.2020

50

54.2

Michigami et al.2020 ++
10 c.1132G>T p.Asp378Tyr Asp361Tyr del Angel et al. 2020 odonto. c.[1132G>T];[=] 0 Michigami et al.2020 Michigami et al.2020 ++
10 c.1132G>C p.Asp378His P Asp361His Whyte et al. 2015 childhood c.[571G>A];[1132G>C] ++
10 c.1133A>T p.Asp378Val P Asp361Val

Henthorn et al. 1992

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

infantile

perinatal

childhood

Prenat. benign

c.[571G>A];[1133A>T]

c.[1133A>T];[1133A>T]

c.[1133A>T;[=]

c.[1133A>T];[=]

1.2

2.1

Lia-Baldini et al. 2001

del Angel et al. 2020

19.9

28.2

Lia-Baldini et al. 2001

del Angel et al. 2020

++
10 c.1133A>G p.Asp378Gly P Asp361Gly Tenorio et al. 2017 c.[1133A>G];[571G>A] ++
10 c.1135C>A p.His379Asn P His362Asn Dr Ivan Iglesias-Baena, CEO
GenActive Clinic & Research,
C / Madrid 79, Monachil, 18193,
Granada, Spain. info@genactive.es
adult c.[1135C>A];[=] ++
10 c.1142A>G p.His381Arg P His364Arg

Taillandier et al. 2000

del Angel et al. 2020

infantile

perinatal

c.[1142A>G];[119C>T]

c.[1142A>G];[814del]

++
10 c.1144G>A p.Val382Ile P Val365Ile

Goseki-Sone et al. 1998

del Angel et al. 2020

childhood

prenat. benign

c.[1144G>A];[979T>C]

c.[1144G>A];[=]

0 Watanabe et al. 2002 30.0 Takinami et al. 2004 ++
10 c.1162T>C p.Tyr388His P Tyr371His

Liu et al. 2010

Yang et al. 2013

odonto

odonto

c.[997+1G>T];[1162T>C]

c.[82T>G];[1162T>C]

39.7 Zhu et al. 2012 60 Yang et al. 2013 ++
10 c.1166C>T p.Thr389Ile P Thr372Ile Versailles lab oct. 2004 perinatal c.[1101_1103del];[1166C>T] ++
10 c.1166C>A p.Thr389Asn P Thr372Asn


Yang et al. 2013

Bai et al. 2016

Versailles lab Jan 2020

childhood

perinatal

perinatal

c.[1166C>A];[407G>T]

c.[1166C>A];[1250A>G]

c.[1166C>A];[1166C>A]

0 Yang et al. 2013

40

Yang et al. 2013 ++
10 c.1171C>T p.Arg391Cys P Arg374Cys

Zurutuza et al. 1999

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

childhood

adult

childhood

infantile

c.[571G>A];[1171C>T]

c.[1171C>T];[N]

c.[1171C>T];[N]

c.[1171C>T];[1042G>A]

10.3

2.2

Zurutuza et al. 1999

del Angel et al. 2020

50.5

55.2

Fauvert et al. 2009

del Angel et al. 2020

++
10 c.1172G>A p.Arg391His P Arg374His

Orimo et al. 2002

del Angel et al. 2020

childhood

adult

c.[1172G>A];[=]

c.[1172G>A];[=]

3.7

2.1

Orimo et al. 2001

del Angel et al. 2020

29.1

20.4

Fauvert et al. 2009

del Angel et al. 2020

++
10 c.1171del p.Arg391Valfs P Arg374Valfs


Taillandier et al. 1999

del Angel et al. 2020

del Angel et al. 2020

infantile

infantile

infantile

c.[184A>T];[1171del]

c.[1171del];[1171del]

c.[1171del];[571G>A]

2.1 del Angel et al. 2020 72.9 del Angel et al. 2020 na
10 c.1175G>C p.Gly392Ala P Gly375Ala Versailles lab. Jan. 2008 perinatal c.[1175G>C];[406C>T] ++
10 c.1178A>T p.Asn393Ile Asn376Ile Versailles lab March 2013 infantile moderate c.[571G>A];[1178A>T] +
10 c.1181_1182del p.Ser394fs P Ser377fs Wenkert et al. 2011 prenatal benign c.[997+3A>G];[1181_1182del] na
10 c.1182dup p.Ile395fs Ile395fs communicated by Dr Rhonda
Singhapong (Alexion)
adult c.[1182dup] ;[=] na
10 c.1183A>G p.Ile395Val P Ile378Val

Wenkert et al. 2011

Katsuyuki et al. 2019

Mornet et al. 2020

prenatal benign

childhood

adult

c.[1183A>G];[457T>C]

c.[1183A>G];[1559del]

c.[1183A>G];[=]

19 Chen et al. 2017 50 Chen et al. 2017 ++
10 c.1184T>C p.Ile395Thr P Ile378Thr Versailles lab Jul. 2006 perinatal c.[1184T>C];[571G>A] ++
IVS10 c.1189+5del P Whyte et al. 2015 childhood c.[1189+5del];[1328C>T] na
11 c.1190G>A p.Gly397Asp P Gly380Asp

Whyte et al. 2015

odonto.

c.[1190G>A];[=]

++
11 c.1190G>T p.Gly397Val Gly380Asp Versailles lab Dec. 2019 childhood (moderate) c.[1190G>T];[=] ++
11 c.1195G>T p.Ala399Ser P Ala382Ser Taillandier et al. 2001 adult c.[1195G>T];[704A>G] ++
11 c.1196C>T p.Ala399Val P Ala382Val

Spentchian et al. 2006

del Angel et al. 2020

adult

perinatal

c.[1196C>T];[98C>T]

c.[1196C>T];[648+2dup]

++
11 c.1199C>T p.Pro400Leu P Pro383Leu Spentchian et al. 2006 infantile c.[1199C>T];[1199C>T] ++
11 c.1214_1215del p.Thr405Argfs P Thr388Argfs Versailles lab Jul. 2006 adult c.[571G>A];[1214_1215del] na
11 c.1216_1219del p.Asp406Argfs P Asp389Argfs Brun-Heath et al. 2005 perinatal c.[1216_1219del];[?] na
11 c.1216G>A p.Asp406Asn Asp389Asn Versailles lab Dec 2011 perinatal c.[952C>T];[1216G>A] -
11 c.1217A>G p.Asp406Gly P Asp389Gly Taillandier et al. 2000 odonto. c.[1217A>G];[1349G>A] 14.9 Taillandier et al. 2000 -
11 c.1228T>C p.Phe410Leu P Phe393Leu Versailles lab oct. 2004 infantile c.[1228T>C];[571G>A] +
11 c.1231A>G p.Thr411Ala P Thr394Ala Brun-Heath et al. 2005 perinatal c.[1231A>G];[928_929del] 0.3 Brun-Heath et al. 2005 ++
11 c.1238T>C p.Ile413Thr p.Ile396Thr University of Brasilia Lab, July 2016 childhood c.[1238T>C];[?] ++
11 c.1240C>A p.Leu414Met P Leu397Met

Mumm et al. 2002

perinatal

c.[1240C>A];[811A>C]

c.[1240C>A];[=]

0.4

5.1

Fauvert et al. 2009

del Angel et al. 2020

23.5

43.7

Fauvert et al. 2009

del Angel et al. 2020

++
11 c.1243T>G p.Tyr415Asp Tyr398Asp Saglam et al. 2017 perinatal c.[1243T>G];[1243T>G] ++
11 c.1244A>G p.Tyr415Cys LP Tyr398Cys Versailles lab March 2020 adult c.[1244A>G];[=] ++
11 c.1250A>G p.Asn417Ser P Asn400Ser

Sergi et al. 2001

Reibet et al. 2009

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

perinatal

odonto

adult

childhood

prenat benign

c.[1250A>G];[648+1G>A]

c.[1250A>G];[=]

c.[1250A>G];[=]

c.[1250A>G];[=]

c.[1250A>G];[=]

3

3.6

Fauvert et al. 2009

del Angel et al. 2020

26.5

31.9

Fauvert et al. 2009

del Angel et al. 2020

++
11 c.1256del p.Pro419Leufs P Pro402Leufs Taillandier et al. 2000 perinatal c.[1256del];[?] na
11 c.1258G>A p.Gly420Ser P Gly403Ser

Glaser et al. 2004

del Angel et al. 2020

perinatal

perinatal

c.[1258G>A];[1258G>A]

c.[1258G>A];[299C>T]

0

3.7

Makita et al. 2012

del Angel et al. 2020

40

31.1

Makita et al. 2012

del Angel et al. 2020

++
11 c.1259G>C p.Gly420Ala P Gly403Ala

Fauvert et al. 2009

del Angel et al. 2020

childhood

odonto

c.[1259G>C];[571G>A]

c.[1259G>C];[=]

4.2 Fauvert et al. 2009 19.7 Fauvert et al. 2009 ++
11 c.1259G>A p.Gly420Asp Gly403Asp

Versailles lab Feb. 2019

del Angel et al. 2020

childhood

childhood

c.[1259G>A];[=]

c.[1259G>A];[407G>A]

4.0 del Angel et al. 2020 34.3 del Angel et al. 2020 ++
11 c.1265A>G p.Lys422Arg Lys405Arg Versailles lab April 2018 adult c.[1265A>G];[=] 78.7 del Angel et al. 2020 80.5 del Angel et al. 2020 +
11 c.1268T>C p.Val423Ala P Val406Ala

Taillandier et al. 2001

del Angel et al. 2020

perinatal

childhood

c.[1268T>C];[346G>A]

c.[1268T>C];[=]

15.7 Numa et al. 2008 +
11 c.1270G>A p.Val424Met P Val407Met Versailles lab jan. 2007 adult c.[1270G>A];[1270G>A] 58.5 del Angel et al. 2020 88.4 del Angel et al. 2020 +
11 c.1271T>C p.Val424Ala P Val407Ala Zhang et al. 2012 adult c.[1271T>C];[1271T>C] +
11 c.1276G>T p.Gly426Cys P Gly409Cys

Mochizuki et al. 2000

infantile

c.[670A>G];[1276G>T]

18.5 Michigami et al. 2005 ++
11 c.1276G>A p.Gly426Ser P Gly409Ser

Versailles lab Apr 2011

Mornet et al. 2020

infantile

adult

c.[1276G>A];[1276G>A]

c.[1276G>A];[=]

10

Al-Shawafi et al. 2016 50 Al-Shawafi et al. 2016 ++
11 c.1277G>A p.Gly426Asp P Gly409Asp Mumm et al. 2002 childhood c.[571G>A];[1277G>A] 0 Al-Shawafi et al. 2016 60 Al-Shawafi et al. 2016 ++
11 c.1282C>T p.Arg428* P Arg411Ter Taillandier et al. 1999 perinatal c.[1282C>T];[1282C>T]

3.3

del Angel et al. 2020 68.9 del Angel et al. 2020 na
11 c.1283G>C p.Arg428Pro P Arg411Pro Spentchian et al. 2006 perinatal c.[997+2T>A];[1283G>C] ++
11 c.1283G>A p.Arg428Gln Arg411Gln

Versailles lab Jul. 2010

del Angel et al. 2020

prenatal benign

childhood

c.[1283G>A];[=]

c.[1283G>A];[=]

4.2 del Angel et al. 2020 48.5 del Angel et al. 2020 ++
11 c.1283G>T p.Arg428Leu Arg411Leu Plendl et al. 2011 adult c.[1283G>T];[?] ++
11 c.1285G>A p.Glu429Lys P Glu412Lys Versailles lab Jul. 2006 odonto. c.[1285G>A];[=] 1.3 Fauvert et al. 2009 31.0 Fauvert et al. 2009 ++
11 c.1289A>G p.Asn430Ser P Asn413Ser Whyte et al. 2015 infantile c.[571G>A];[1289A>G] 0 Komaru et al. 2016

58

Komaru et al. 2016 ++
11 c.1292T>A p.Val431Asp LP Val414Asp Esmel-Vilomara et al. 2019 childhood HPP (diagnosed at birth) c.[1292T>A];[=] +
11 c.1292T>C p.Val431Ala P Val414Ala Taillandier et al. 2015 odonto. c.[1292T>C];[=] +
11 c.1306T>C p.Tyr436His P Tyr419His Henthorn et al. 1992 childhood c.[98C>T];[1306T>C] ++
11 c.1307A>G p.Tyr436Cys P Tyr419Cys Taketani et al. 2013 infantile c.[1307A>G];[1559del] ++
11 c.1307A>C p.Tyr436Ser Tyr419Ser Nielson et al. 2012 asymptomatic*, low BMD c.[1307A>C];[=] ++
12 c.1313A>T p.His438Leu P His421Leu del Angel et al. 2020 perinatal survival c[.1313A>T];[1313A>T] ++
12 c.1318_1320 del p.Asn440del P Asn423del Martins et al. 2013 odonto. c.[454C>T];[1318_1320del] na
12 c.1323C>A p.Tyr441* P Tyr424* Hofmann et al. 2013 perinatal c.[667C>T];[1323C>A] 1.0 Hofmann et al. 2013 58.3 Hofmann et al. 2013 na
12 c.1327G>A p.Ala443Thr Ala426Thr Garcia-Fontana et al. 2019 Adult c.[1327G>A];[=] 7.0 del Angel et al. 2020 72.9 del Angel et al. 2020 ++
12 c.1328C>T p.Ala443Val P Ala426Val

Fauvert et al. 2009

Mornet et al 2020

adult

childhood

c.[1328C>T];[=]

c.[1328C>T];[=]

1.4

7.7

Fauvert et al. 2009

del Angel et al. 2020

53.1

57.4

Fauvert et al. 2009

del Angel et al. 2020

++
12 c.1328C>A p.Ala443Glu P Ala426Glu Khandwala et al. 2006 adult c.[1328C>A];[=] ++
12 c.1333T>C p.Ser445Pro P12 Ser428Pro

Mornet et al. 1998

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

infantile

infantile

adult

odonto


c.[1333T>C];[?]

c.[1333T>C];[407G>A]

c.[1333T>C];[=]

c.[1333T>C];[=]

2.1 Zurutuza et al. 1999 35.1 Fauvert et al. 2009 +
12 c.1336G>A p.Ala446Thr P Ala429Thr Versailles lab Jan 2013 perinatal c.[1336G>A];[1336G>A] ++
12 c.1348C>T p.Arg450Cys P Arg433Cys

Mornet et al. 1998

del Angel et al. 2020

infantile

perinatal

c.[1348C>T];[1348C>T]

c.[1348C>T];[1348C>T]

4.0

11.2

Zurutuza et al. 1999

del Angel et al. 2020

101 del Angel et al. 2020 +
12 c.1349G>A p.Arg450His P Arg433His Taillandier et al. 2000 odonto. c.[1217A>G];[1349G>A]
12 c.1354G>A p.Glu452Lys P Glu435Lys

Spentchian et al. 2003

del Angel et al. 2020

perinatal

adult

c.[1354G>A];[331G>A]

c.[1354G>A];[=]

1.4

4.1

Fauvert et al. 2009

del Angel et al. 2020

27.5

32.3

Fauvert et al. 2009

del Angel et al. 2020

++
12 c.1361A>G p.His454Arg P His437Arg Versailles lab oct. 2003 childhood c.[571G>A];[1361A>G] 2.4 del Angel et al. 2020 36.9 del Angel et al. 2020 ++
12 c.1363G>A p.Gly455Ser P Gly438Ser

Draguet et al. 2004

adult

c.[1363G>A];[1471G>A]

71.0

1.19

Brun-Heath et al. 2007

del Angel et al. 2020

1.19 del Angel et al. 2020 ++
12 c.1364G>A p.Gly455Asp P Gly438Asp Versailles lab jan. 2007 perinatal c.[1364G>A];[1364G>A] ++
12 c.1366G>T p.Gly456Trp P Gly439Trp Versailles lab oct. 2003 childhood c.[1366G>T];[?] 0.8 Fauvert et al. 2009 14.5 Fauvert et al. 2009 ++
12 c.1366G>A p.Gly456Arg Gly439Arg

Ozono et al. 1996

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

Yokoi et al. 2019

infantile

infantile

childhood

odonto

mild/moderate



c.[1366G>A];[?]

c.[1366G>A];[881A>C]

c.[1366G>A];[=]

c.[1366G>A];[=]

c.[1366G>A];[=]

1.5

2.5

Fauvert et al. 2009

ddel Angel et al. 2020

50.5

42.2

Fauvert et al. 2009

del Angel et al. 2020

++
12 c.1367G>A p.Gly456Glu Gly439Glu Versailles lab. Dec 2018 Odonto childhood c.[1367G>A];[=] 4.8 del Angel et al. 2020 30.9 del Angel et al. 2020 ++
12 c.1372G>A p.Asp458Asn Asp441Asn Versailles lab Dec 2011 adult c.[571G>A];[372G>A] ++
12 c.1373A>G p.Asp458Gly Asp441Gly Plendl et al. 2011 infantile c.[571G>A];[1373A>G] ++
12 c.1375G>A p.Val459Met P Val442Met

Taillandier et al. 2000

Whyte et al. 2016

infantile

infantile

c.[152C>T];[1375G>A]

c.[252G>C];[1375G>A]

++
12 c.1375G>T p.Val459Leu P Val442Leu Versailles lab oct. 2004

perinatal

odonto

c.[1354G>A];[1375G>T]

c[1375G>T];[=]

0 Fauvert et al. 2009 41.1 Fauvert et al. 2009 ++
12 c.1376T>C p.Val459Ala Val442Ala Xu et al. 2018 adult c.[1376T>C];[=] ++
12 c.1381G>A p.Val461Ile LP Val444Ile

Nielson et al. 2012

del Angel et al. 2020

asymptomatic*, low BMD

adult

c.[1381G>A];[?]

c.[1381G>A];[=]

80.1 del Angel et al. 2020 89.0 del Angel et al. 2020 +
12 c.1397C>T p.Pro466Leu P Pro449Leu Versailles lab oct. 2003 perinatal c.[1397C>T];[?] 5.7 del Angel et al. 2020 51.8 del Angel et al. 2020 +
12 c.1400T>C p.Met467Thr P Met450Thr Versailles lab oct. 2004 infantile c.[919C>T];[1400T>C] +
12 c.1402G>A p.Ala468Thr P Ala451Thr

Spentchian et al. 2003

del Angel et al. 2020

perinatal

infantile

c.[1402G>A];[1402G>A]

c.[1402G>A];[1402G>A]

5.6 del Angel et al. 2020 78.7 del Angel et al. 2020 ++
12 c.1403C>T p.Ala468Val Ala451Val Taillandier et al. 2017 adult c.[1403C>T];[=] 3.9 del Angel et al. 2020 64.9 del Angel et al. 2020 ++
12 c.1412_1429del p.Leu471_Glu476del Leu454_Glu459del Plendl et al. 2011 adult c.[1412_1429del];[?] na
12 c.1414C>T p.His472Tyr His455Tyr V. Buzzi, P. La Verde, Milan, Italy perinatal c.[299C>T];[1414C>T] ++
12 c.1417G>A p.Gly473Ser P Gly456Ser

Mornet et al. 1998

Martins et al. 2019

perinatal

adult

c.[1417G>A];[119C>T]

c.[1417G>A];[1460C>T]

++
12 c.1418G>A p.Gly473Asp Gly456Asp Nakamura-Utsunomiya et al. 2010 perinatal c.[1418G>A];[1559del] ++
12 c.1418_1438dup p.Gly473_Tyr479dup LP Gly456_Tyr62dup Versailles lab Dec. 2019 asymptomatic c.[1418_1438dup];[=] na
12 c.1426G>A p.Glu476Lys P Glu459Lys

Taillandier et al. 1999

del Angel et al. 2020

del Angel et al. 2020

perinatal

infantile

adult

c.[1426G>A];[331G>A]

c.[1426G>A];[571G>A]

c.[1426G>A];[=]

4.3 del Angel et al. 2020 37.5 del Angel et al. 2020 ++
12 c.1426G>T p.Glu476* Glu459* Clinvar (Counsyl) infantile not provided ++
12 c.1427A>G p.Glu476Gly P Glu459Gly Mornet et al. 2001 perinatal c.[1427A>G];[1427A>G] ++
12 c.1427A>C p.Glu476Ala P Glu459Ala Versailles lab March 2009 adult c.[1427A>C];[?] 0.4 Fauvert et al. 2009 39.3 Fauvert et al. 2009 ++
12 c.1433A>T p.Asn478Ile P Asn461Ile

Taillandier et al. 2000

del Angel et al. 2020

childhood

odonto

c.[1433A>T];[=]

c.[1433A>T];[=]

1.1 Lia-Baldini et al. 2001 38.2 Lia-Baldini et al. 2001 ++
12 c.1444C>A p.His482Asn P His465Asn Nielson et al. 2012 asymptomatic*, low BMD c.[1444C>A];[=] 91.8 del Angel et al. 2020 108 del Angel et al. 2020 ++
12 c.1444dup p.His482Profs His465Profs Brun-Heath et al. 2005 perinatal c.[1444dup];[1001G>A] na
12 c.1447G>A p.Val483Met Val466Met Research center for medical genetics,
Moscow, Aug. 2016
childhood c.[1447G>A];[?] +
12 c.1460C>T p.Ala487Val P Ala470Val

Taillandier et al. 2015

Martins et al. 2019

perinatal

adult

c.[1460C>T];[.984_986del]

c.[1417C>T];[1460C>T]

++
12 c.1466G>C p.Cys489Ser P Cys472Ser Taillandier et al. 2000 perinatal c.[997+2T>A];[1466G>C]

9.4

6.8

Taillandier et al. 2000

del Angel et al. 2020

58.4 del Angel et al. 2020 ++
12 c.1468A>T p.Ile490Phe P Ile473Phe Lia-Baldini et al. 2001 adult c.[1468A>T];[?] 37.1 Lia-Baldini et al. 2001 77.4 Lia-Baldini et al. 2001 +
12 c.1471G>A p.Gly491Arg P Gly474Arg

Mornet et al. 1998

del Angel et al. 2020

del Angel et al. 2020

del Angel et al. 2020

Mornet et al. 2020

Yokoi et al. 2019

perinatal

perinatal

perinatal

perinatal

adult

mild/moderate

c.[1471G>A];[385G>A]

c.[1471G>A];[1471G>A]

c.[1471G>A];[203C>T]

c.[1471G>A];[303_311del]

c.[1471G>A];[=]

c.[1471G>A];[c.283G>A]

7.8 del Angel et al. 2020 72.8 del Angel et al. 2020 ++
12 c.1474del p.Ala492Profs P Ala475Profs

Brun-Heath et al. 2005

Galeano-Valle et al. 2019

del Angel et al. 2020

odonto

adult

perinatal

c.[1474del];[407G>A]

c.[1474del];[=]

c.[1474del];[668G>A]

na
12 c.1479C>A p.Asn493Lys P Asn476Lys Porntaveetus et al. 2017 infantile c.[1460C>T];[1479C>A] -
12 c.1483G>A p.Gly495Ser VUS Gly478Ser Michigami et al.2020 infantile c.[1483G>A];[1483G>A] 72.5 del Angel et al. 2020 80.0 del Angel et al. 2020 -
12 c.1489T>A p.Cys497Ser Cys480Ser Xu et al. 2018 adult c.[1489T>A];[=] ++
12 c.1530_1549del p.Leu512Profs Leu495Profs Clinvar (Counsyl) infantile not provided na
12 c.1540G>A p.Ala514Thr

VUS

Ala497Thr Tenorio et al. 2017 infantile c.[1540G>A];[407G>A] 96.2 del Angel et al. 2020 94.8 del Angel et al. 2020 +
12 c.1553_1569del p.Tyr518Phefs Tyr501Phefs Versailles lab nov. 2009 perinatal c.[1553_1569del];[881A>C] na
12 c.1554C>A p.Tyr518* Tyr501* Dr S. Monnot, Necker Hospital,
Paris, France, Feb. 2019
perinatal c.[1554C>A];[1554C>A] 6.0 del Angel et al. 2020 60.2 del Angel et al. 2020 na
12 c.1559del p.Leu520Argfs P Leu503Argfs

Orimo et al. 1994

Yokoi et al. 2019

Michigami et al.2020

Michigami et al.2020

Michigami et al.2020

Michigami et al.2020

Michigami et al.2020

infantile

odonto childhood

perinatal severe

perinatal benign

odonto

odonto

odonto


c.[892G>A];[1559del]

c.[1183A>G];[1559del]

c.[1559del];[1559del]

c.[572A>G];[1559del]

c.[704A>T];[1559del]

c.[407G>A];[1559del]

c.[979T>C];[1559del]

28

5.6

Komaru et al. 2008

del Angel et al. 2020

82.2 del Angel et al. 2020 na
12 c.*124_126delinsAG VUS Versailles lab Sept 2019 adult c.[124_126delinsAG] na


Large deletions/duplications
Due to the incertainty of borders, all large deletions/duplications submitted to the database will be included. However, each type will be counted only once.

deletion of exon 1 Versailles lab July 2012 perinatal homozygote na

3kb deletion in IVS1

g.(15599_18599)del Versailles lab Oct. 2016 infantile

compound heterozygote with
deletion exon 1 - IVS1 - exon 2

na
deletion exon 1 - IVS1 - exon 2 g.(1-54621_1-35638)_(44833_46877)del Versailles lab May 2016 infantile compound heterozygote with 3kb deletion in IVS1 na
deletion of exon 2 g.(16650_17870)_(48651_50859)del Versailles lab July 2013 perinatal homozygote na
deletion of exon 2 H Mateus, Alexion Pharmaceuticals, Colombia infantile compound heterozygote with c.[382G>A] na
deletion of exon 2 g.(42056_43422)_(46936_47669)del Versailles lab Nov. 2018 adult heterozygote na
del IVS3 Whyte et al. 2015 odonto. heterozygote na
deletion exons 2-6 Dr I. Rau , Institut für Humangenetik, Hamburg, Germany adult heterozygote na
duplication of exons 2-6 P Hacihamdioglu et al. 2018 perinatal homozygote na
deletion of exons 3-5(?) g.(44834_46878)_(51650_52773)del P Spentchian et al. 2006 perinatal homozygote na
indel in exon 5 Whyte et al. 2015 odonto. heterozygote na
deletion of exon 5 Versailles lab April 2018 adult heterozygote na
deletion exon 9 g.(?_64307)_(64441_?)del P Versailles lab Dec. 2015 prenat. benign compound heterozygote with c.407G>A na
deletion of exon 12 (3' part) P

Spentchian et al. 2006

infantile compound heterozygote
with c.542C>T
na

* Phenotype "asymptomatic": repeatedly low serum alkaline phosphatase, no hypophosphatasia clinical symptom

Statistics

Type of mutation Number of mutations %
Missense 292 71.0
Small deletions 45 11.0
Splicing 20 4.9
Nonsense 20 4.9
Small insertions 14 3.4
Large del/dup 12 2.9
Ins/Del 6 1.5
Regulatory 2 0.5
Total 411 100
Distribution of mutations in exons


Legend to database items
  • Nomenclature : see the nomenclature section below.
  • Reference : reference of the publication reporting the mutation.
  • Pathogenicity: : classification of the variant according to Richards et al. (2015) and Karbassi et al. (2015). The classification give a score of pathogenicity : B benign; LB likely benign; VUS variant of unknown significance; LP likely pathogenic; P pathogenic
  • Clinical form : clinical form of the patient in whom the mutation was detected for the first time.
  • Genotype : genotype of the patient in whom the mutation was detected for the first time.
  • ? : uncharacterized allele (only one detected mutation without molecular, pedigree, or in silico evidence of dominant transmission).
  • N : normal allele (dominant mutation on the other chromosome, evidenced by molecular, pedigree, or in silico data.
  • %WT : residual activity of the mutant protein. Alkaline phosphatase activity of cells transfected with mutant cDNAs, expressed in percentage of the activity found in cells transfected with wild type (WT) cDNA.
  • % 50/50 : dominant negative effect of the mutation. Alkaline phosphatase activity of cells co-transfected with equal quantities of wild type and mutant cDNAs, expressed in percentage of the activity found in cells transfected with wild type (WT) cDNA. For mutations producing no residual activity, the value is expected to be 50% if there is no dominant negative effect, and <50% if there is a dominant negative effect (Lia-Baldini et al. 2001).
  • unp. : unpublished.
  • Conservation : conservation of the affected amino acid among 58 mammalian TNSALP according to Silvent et al. (2014). ++ conserved residue ; + conservative changes only, - residue not conserved, na not applicable.

Nomenclature

  • Nucleotides numbering is given according to Weiss et al. 1988, the Nomenclature Working Group (S.E. Antonarakis and the Nomenclature Working Group, Hum. Mut. 11:1-3, 1998) and the HGVS recommendations: the first nucleotide (+1) corresponds to the A of the ATG initiation codon. Reference transcript: ENST00000374840.8 / NM_00478.6.)
  • Amino acids numbering is given according to both the standardized and the non-standardized nomenclatures.
    The standardized nomenclature follows the HGVS recommendations: the first codon is the ATG initiation codon.
    The non-standardized nomenclature was used in publications before 2008-2009 : this nomenclature takes into account of a 17-residues signal peptide, i.e. the ATG initiation codon is numbered as residue minus (-)17 (Weiss et al. 1988).
  • p: protein numbering; c: nucleotide numbering of the coding sequence.

References: