Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes.

Human Molecular Genetics
Mika Asai-CoakwellOrdan J Lehmann

Abstract

Proteins of the bone morphogenetic protein (BMP) family are known to have a role in ocular and skeletal development; however, because of their widespread expression and functional redundancy, less progress has been made identifying the roles of individual BMPs in human disease. We identified seven heterozygous mutations in growth differentiation factor 6 (GDF6), a member of the BMP family, in patients with both ocular and vertebral anomalies, characterized their effects with a SOX9-reporter assay and western analysis, and demonstrated comparable phenotypes in model organisms with reduced Gdf6 function. We observed a spectrum of ocular and skeletal anomalies in morphant zebrafish, the latter encompassing defective tail formation and altered expression of somite markers noggin1 and noggin2. Gdf6(+/-) mice exhibited variable ocular phenotypes compatible with phenotypes observed in patients and zebrafish. Key differences evident between patients and animal models included pleiotropic effects, variable expressivity and incomplete penetrance. These data establish the important role of this determinant in ocular and vertebral development, demonstrate the complex genetic inheritance of these phenotypes, and further understanding of BMP...Continue Reading

References

Sep 1, 1989·Human Genetics·D N Cooper, M Krawczak
Feb 1, 1988·Human Genetics·D N Cooper, H Youssoufian
Nov 12, 1965·Science·M R Urist
Jan 1, 1981·Survey of Ophthalmology·R A Pagon
Mar 1, 1996·Nature Genetics·J T ThomasF P Luyten
Jan 10, 1997·Experimental Cell Research·N JenaC M Croce
Sep 1, 1997·Nature Genetics·A PolinkovskyM L Warman
Dec 16, 1998·Genes & Development·Y Furuta, B L Hogan
Aug 10, 2000·Nature Genetics·E Ferda PercinR R McInnes
Sep 6, 2000·Nature Genetics·UNKNOWN International PPH ConsortiumR C Trembath
Jul 10, 2002·The Journal of Cell Biology·Andrea D WestonT Michael Underhill
Nov 15, 2002·Developmental Cell·Andrew Jan WaskiewiczCecilia B Moens
Feb 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Samuel SidiFrédéric M Rosa
May 2, 2003·American Journal of Human Genetics·Noriyuki AzumaMasao Yamada
Sep 17, 2003·Genes & Development·Kai JiaoBrigid L M Hogan
Oct 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Katarina LehmannStefan Mundlos
Oct 4, 2003·Nature Reviews. Genetics·Kristin A Waite, Charis Eng
Apr 6, 2004·Developmental and Comparative Immunology·Amaury HerpinPascal Favrel
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wei LiuJames F Martin
Dec 29, 2004·Growth Factors·Di ChenGregory R Mundy
Jan 27, 2005·The Journal of Biological Chemistry·Tarek A SamadClifford J Woolf
Apr 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Osamu HashimotoShunichi Shimasaki
Apr 23, 2005·American Journal of Human Genetics·Nicola K RaggeIsabel M Hanson
Jun 7, 2005·Developmental Biology·Wei LiuJames F Martin

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Citations

Jan 12, 2013·Human Molecular Genetics·Mika Asai-CoakwellOrdan J Lehmann
Jan 25, 2014·Biologicals : Journal of the International Association of Biological Standardization·Lisa A WilliamsAshish D Diwan
Aug 10, 2010·Annual Review of Genomics and Human Genetics·Dustin BaldridgeBrendan Lee
Oct 30, 2009·Human Molecular Genetics·Ming YeOrdan J Lehmann
Jul 18, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Aiqun WeiAshish D Diwan
Oct 15, 2011·Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie·Christopher J RudniskyIan M MacDonald
Nov 11, 2009·Cytokine & Growth Factor Reviews·Steven Pregizer, Douglas P Mortlock
Sep 21, 2011·Birth Defects Research. Part C, Embryo Today : Reviews·Ann C Morris
Jun 27, 2013·Wiley Interdisciplinary Reviews. Developmental Biology·Walter L EckalbarKenro Kusumi
Nov 21, 2012·American Journal of Medical Genetics. Part a·Benjamin D SolomonPhilip F Giampietro
Aug 5, 2010·Human Mutation·Ashley M ByrnesDennis E Bulman
Mar 5, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Nykolaus P Reed, Douglas P Mortlock
May 27, 2014·European Journal of Medical Genetics·Kathleen A Williamson, David R FitzPatrick
Dec 9, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jian WangYiping Shen
Jun 6, 2015·Birth Defects Research. Part C, Embryo Today : Reviews·Linda M Reis, Elena V Semina
May 28, 2011·Clinical Science·Juan F SantibañezCarmelo Bernabeu
Oct 19, 2011·Molecular Genetics and Metabolism·Anne M Slavotinek
Aug 28, 2012·Developmental Biology·Renee Kruse-BendChi-Bin Chien
Sep 21, 2010·Biochimica Et Biophysica Acta·Patricia A GongalAndrew J Waskiewicz
Jan 10, 2012·American Journal of Human Genetics·Lejin WangZhenglin Yang
Feb 27, 2015·PLoS Genetics·Brett DemlElena V Semina
Jan 18, 2017·European Journal of Human Genetics : EJHG·Rose RichardsonMariya Moosajee
Nov 14, 2017·American Journal of Medical Genetics. Part a·Paulien A TerhalGijs van Haaften
Jul 25, 2018·Congenital Anomalies·Hideyo OhuchiTetsuya Bando
Dec 30, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Shlomo KrispinBrant M Weinstein
Aug 28, 2020·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Kevin H YoonAndrew J Waskiewicz
May 15, 2013·International Journal of Molecular Medicine·Gabriel C DworschakMichael Ludwig
Dec 5, 2017·The Journal of Clinical Investigation·Arvind M VenkatesanCraig J Ceol

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