A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II
A novel mutation in the MITF may be digenic with GJB2 mutations in a large Chinese family of Waardenburg syndrome type II
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MITF 中的一个新突变可能与 II 型瓦登堡综合征中国大家族中的 GJB2 突变是双基因的。
DOI：
10.1016/j.jgg.2011.11.003
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发表时间：
2011-12-01
影响因子：
5.9
通讯作者：
Li, Huawei
中科院分区：
文献类型：
--
作者：
Yan, Xukun;Zhang, Tianyu;Li, Huawei
瓦登堡综合征II型(WS2)与综合征性耳聋有关。WS2的一个子集，WS2a，约占患者的15%，被归因于小眼炎相关转录因子(MITF)基因的突变。我们在一个中国大家庭中研究了WS2的遗传基础。对MITF基因的全部9个外显子、最常见的遗传性耳聋基因GJB2的单个编码外显子(外显子2)和线粒体DNA(MtDNA)12S rRNA进行了测序。MITF基因外显子8的一个新的杂合突变c.[742_743delAAinsT；746_747delCA]与WS2在该家族中共分离。MITF突变导致提前终止密码子和截短MITF蛋白，仅有419个野生型氨基酸中的247个。先证者存在MITF基因杂合性突变和GJB2基因c.[109G>；A]+[235delC]复合杂合性致病突变。该家系未发现线粒体12S rRNA致病突变。因此，MITF外显子8中一个新的复合杂合性突变c.[742_743delAinsT；746_747delCA]是该家系WS2的主要遗传原因，MITF和GJB2基因的双基因效应可能与先证者的耳聋有关。
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 the MITF 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 the GJB2 gene. No pathogenic mutation was found in mtDNA 12S rRNA in this family. Thus, a novel compound heterozygous mutation, c.[742_743delAAinsT; 746_747delCA] in MITF 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.