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

Xukun Yan^{a, b},
Tianyu Zhang^a,
Zhengmin Wang^a,
Yi Jiang^c,
Yan Chen^d,
Hongyan Wang^e,
Duan Ma^e,
Lei Wang^{e
, ,},
Huawei Li^{a, e
, ,}

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)

摘要

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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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doi: 10.1016/j.jgg.2011.11.003

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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

Corresponding author: E-mail address: wanglei2004sjtu@gmail.com (Lei Wang); E-mail address: hwli@shmu.edu.cn (Huawei Li)

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doi: 10.1016/j.jgg.2011.11.003

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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

Corresponding author: E-mail address: wanglei2004sjtu@gmail.com (Lei Wang); E-mail address: hwli@shmu.edu.cn (Huawei Li)

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