A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II

Xukun Yan; Tianyu Zhang; Zhengmin Wang; Yi Jiang; Yan Chen; Hongyan Wang; Duan Ma; Lei Wang; Huawei Li

doi:10.1016/j.jgg.2011.11.003

Volume 38 Issue 12

Dec. 2011

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Article Navigation > Journal of Genetics and Genomics > 2011 > 38(12): 585-591

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A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II

doi: 10.1016/j.jgg.2011.11.003

a
Department of Otolaryngology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031, China
b
Department of Otolaryngology, PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
c
Department of Ophthalmology, Pudong Hospital, 1800 Yuntai Road, Shanghai 200125, China
d
Central Laboratory, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200031,China
e
Institutes of Biomedical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China

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Corresponding author: E-mail address: wanglei2004sjtu@gmail.com (Lei Wang); E-mail address: hwli@shmu.edu.cn (Huawei Li)
Received Date: 2011-06-15
Accepted Date: 2011-11-15
Rev Recd Date: 2011-11-06

Available Online: 2011-11-22

Publish Date: 2011-12-20

Abstract

Abstract

Waardenburg syndrome type II (WS2) is associated with syndromic deafness. A subset of WS2, WS2A, accounting for approximately 15% of patients, is attributed to mutations in the microphthalmia-associated transcription factor (MITF) gene. We examined the genetic basis of WS2 in a large Chinese family. All 9 exons of the MITF gene, the single coding exon (exon 2) of the most common hereditary deafness gene GJB2 and the mitochondrial DNA (mtDNA) 12S rRNA were sequenced. A novel heterozygous mutation c.[742_743delAAinsT;746_747delCA] in exon 8 of theMITF gene co-segregates with WS2 in the family. The MITF mutation results in a premature termination codon and a truncated MITF protein with only 247 of the 419 wild type amino acids. The deaf proband had this MITF gene heterozygous mutation as well as a c.[109G>A]+[235delC] compound heterozygous pathogenic mutation in theGJB2 gene. No pathogenic mutation was found in mtDNA 12S rRNA in this family. Thus, a novel compound heterozygous mutation, c.[742_743delAAinsT;746_747delCA] inMITF exon 8 was the key genetic reason for WS2 in this family, and a digenic effect of MITF and GJB2 genes may contribute to deafness of the proband.
- Waardenburg syndrome type II,
- Hearing loss,
- Mutation

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References(25)

References

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