Evidence suggesting digenic inheritance of Waardenburg syndrome type II with ocular albinism

American Journal of Medical Genetics. Part a
Pei-Wen ChiangTracy L McGregor

Abstract

Waardenburg syndrome (WS) is a series of auditory-pigmentary disorders inherited in an autosomal dominant manner. In most patients, WS2 results from mutations in the MITF gene. MITF encodes a basic helix-loop-helix transcription factor that activates transcription of tyrosinase and other melanocyte proteins. The clinical presentation of WS is highly variable, and we believe that Tietz syndrome and WS2 with ocular albinism (OA) are likely two variations of WS2 due to the presence of modifiers. One family with a molecular diagnosis of WS2 co-segregating with OA has previously been reported. A digenic mutation mechanism including both a MITF mutation and the TYR(R402Q) hypomorphic allele was proposed to be the cause of OA in this family. Here, we present a second WS2 family with OA and provide evidence suggesting the TYR(R402Q) allele does not cause OA in this family. We hypothesize the presence of a novel OCA3 mutation together with the MITF del p.R217 mutation account for the OA phenotype in this family. Since MITF is a transcription factor for pigmentation genes, a mutation in MITF plus a heterozygous mutation in OCA3 together provide an adverse effect crossing a quantitative threshold; therefore, WS2 with OA occurs. We have hy...Continue Reading

References

Jan 2, 1995·American Journal of Medical Genetics·X Z LiuA P Read
Apr 18, 1998·Clinical Dysmorphology·J AmielR M Winter
Jun 14, 2000·Journal of Medical Genetics·S D SmithD Hoover
Feb 24, 2007·American Journal of Medical Genetics. Part a·Thomas SchwarzbraunPeter M Kroisel
Nov 14, 2007·American Journal of Human Genetics·Nadege BondurandVeronique Pingault
Mar 11, 2008·Investigative Ophthalmology & Visual Science·Saunie M Hutton, Richard A Spritz
May 2, 2008·American Journal of Medical Genetics. Part a·Pei-Wen ChiangAnne Chun-Hui Tsai
Aug 6, 2008·American Journal of Medical Genetics. Part a·Pei-Wen ChiangFuki M Hisama
Oct 18, 2008·American Journal of Medical Genetics. Part a·Pei-Wen ChiangCarol L Clericuzio
Feb 12, 2009·American Journal of Medical Genetics. Part a·William S OettingRichard A King
Jun 18, 2009·American Journal of Medical Genetics. Part a·Pei-Wen ChiangAnne Chun-Hui Tsai
Jun 18, 2009·American Journal of Medical Genetics. Part a·Pei-Wen ChiangAngela Scheuerle

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Citations

Feb 4, 2010·Human Mutation·Véronique PingaultNadège Bondurand
Feb 9, 2017·Ophthalmic Genetics·Morgan BertschArlene V Drack
Jan 29, 2021·BioMed Research International·Rong YuLiang-Liang Fan
Sep 28, 2021·Klinische Monatsblätter für Augenheilkunde·Dominik KnebelSiegfried Priglinger

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