New GJA8 variants and phenotypes highlight its critical role in a broad spectrum of eye anomalies

Human Genetics
Fabiola CeroniN K Ragge

Abstract

GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the formation of lens gap junctions. GJA8 mutations have been linked to early onset cataracts in humans and animal models. In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth. Following screening of GJA8 in a cohort of 426 individuals with severe congenital eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven families. Five of these co-segregated with cataracts and microphthalmia, whereas the variant p.(Gly94Arg) was identified in an individual with congenital aphakia, sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or unlikely clinical significance were also identified. Furthermore, the screening of GJA8 structural variants in a subgroup of 188 individuals identified heterozygous 1q21 microdeletions in five families with coloboma and other ocular and/or extraocular findings. However, the exact genotyp...Continue Reading

References

Sep 24, 1998·Current Eye Research·E C SteeleR L Church
Jan 26, 2005·Current Biology : CB·Mariann Bienz
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Jan 16, 2007·Experimental Eye Research·June ChungEric C Beyer
Jul 3, 2007·Journal of Medical Genetics·Surya Prakash G PonnamChitra Kannabiran
Aug 29, 2007·Investigative Ophthalmology & Visual Science·Lars HansenThomas Rosenberg
Aug 1, 2008·Nature·Hreinn StefanssonKari Stefansson
Sep 12, 2008·The New England Journal of Medicine·Heather C MeffordEvan E Eichler
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Aug 27, 2009·Human Mutation·Sibel Ugur IseriNicola K Ragge
Jan 12, 2010·Annual Review of Medicine·Paweł Stankiewicz, James R Lupski
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Feb 6, 2010·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·C-T HuangP-R Hsueh
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 25, 2010·Investigative Ophthalmology & Visual Science·Shaheen P ShahUNKNOWN Surveillance of Eye Anomalies (SEA-UK) Special Interest Group
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Sep 3, 2010·Human Molecular Genetics·Santhosh Girirajan, Evan E Eichler
Sep 16, 2010·European Journal of Clinical Investigation·Anna PfennigerBrenda R Kwak
Dec 15, 2010·PLoS Computational Biology·Eugene V DavydovSerafim Batzoglou
Jan 14, 2011·American Journal of Physiology. Cell Physiology·Jun-Jie TongLisa Ebihara
Mar 1, 2011·American Journal of Ophthalmology·Irina BalikovaJoris Robert Vermeesch
Apr 2, 2011·The Journal of Biological Chemistry·Jialu LiuJean X Jiang
Oct 19, 2011·Molecular Genetics and Metabolism·Anne M Slavotinek
Nov 8, 2011·Ophthalmology·Shaheen P ShahUNKNOWN Surveillance of Eye Anomalies Special Interest Group
Feb 10, 2012·European Journal of Human Genetics : EJHG·Jill A RosenfeldUNKNOWN 1q21.1 Study Group
Jan 26, 2013·Investigative Ophthalmology & Visual Science·Zhen WangKevin L Schey
Nov 10, 2013·Investigative Ophthalmology & Visual Science·Viviana M BerthoudEric C Beyer
Nov 28, 2013·European Journal of Human Genetics : EJHG·Ivan ProkudinRobyn V Jamieson
Jun 8, 2014·Bioinformatics·Lisle E MoseJoel S Parker
Aug 26, 2014·Ophthalmology·Rachel L GillespieI Christopher Lloyd
Feb 24, 2015·Investigative Ophthalmology & Visual Science·Patricia Fernandez-San JoseCarmen Ayuso
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Jun 6, 2015·Birth Defects Research. Part C, Embryo Today : Reviews·Linda M Reis, Elena V Semina
Jun 13, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Raphael BernierUNKNOWN Simons VIP consortium

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Citations

Mar 29, 2020·The British Journal of Ophthalmology·Vanita BerryMichel Michaelides
Oct 7, 2018·Human Genetics·Julie PlaisanciéM Corton
Aug 15, 2020·Orphanet Journal of Rare Diseases·Andrey V MarakhonovMarta Corton
Aug 9, 2019·Human Genetics·Patrick CalvasNicola Ragge
Mar 7, 2021·International Journal of Molecular Sciences·Philippa HardingMariya Moosajee

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Methods Mentioned

BETA
exome sequencing
PCR
Genotyping
Assay

Software Mentioned

Vertebrate Multiz Browser
Polyphen
PhyloP
gnomAD
SIFT
dbNSFP

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