Molecular etiology and genotype-phenotype correlation of Chinese Han deaf patients with type I and type II Waardenburg Syndrome.
Molecular etiology and genotype-phenotype correlation of Chinese Han deaf patients with type I and type II Waardenburg Syndrome.
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中国汉族I型和II型Waardenburg综合征聋哑患者的分子病因及基因型-表型相关性
DOI：
10.1038/srep35498
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发表时间：
2016-10-19
影响因子：
4.6
通讯作者：
Yang T
中科院分区：
文献类型：
--
作者：
Sun L;Li X;Shi J;Pang X;Hu Y;Wang X;Wu H;Yang T
以感音神经性耳聋和色素异常为特征的Waardenburg综合征(WS)具有遗传异质性和表型变异。本研究对36名中国汉族聋人先证者和16名临床诊断为WS I型(Ws1，n = 8)和II型(Ws2，n = 42)的家系成员进行了WS的分子病因学和基因-表型相关性研究。6个WS相关基因的突变筛选在7个WS1先证者中有6个(86%)检测到PAX3突变。29例WS2先证者中，SOX10突变13例(45%)，MITF突变10例(34%)。在检测到的26个突变中，有19个是新的。在有父母DNA样本的WS2先证者中，SOX10突变(7/8)频繁发生，而MITF突变则不常见(0/5，P= 0.005)。中国汉族人WS2MITF突变先证者(7/10)多发雀斑，SOX10突变先证者(0/13，P= 4.9 × 10−4)多发雀斑。我们的结果表明，SOX10和MITF突变是WS2相关耳聋的两个主要原因。这两种WS2亚型可以通过SOX10突变的高新发率和与MITF突变相关的过度雀斑表型来区分。
Waardenburg syndrome (WS) characterized by sensorineural hearing loss and pigmentary abnormalities is genetically heterogeneous and phenotypically variable. This study investigated the molecular etiology and genotype-phenotype correlation of WS in 36 Chinese Han deaf probands and 16 additional family members that were clinically diagnosed with WS type I (WS1, n = 8) and type II (WS2, n = 42). Mutation screening of six WS-associated genes detectedPAX3mutations in 6 (86%) of the 7 WS1 probands. Among the 29 WS2 probands, 13 (45%) and 10 (34%) were identified withSOX10andMITFmutations, respectively. Nineteen of the 26 detected mutations were novel. In WS2 probands whose parental DNA samples were available,de novomutations were frequently seen forSOX10mutations (7/8) but not forMITFmutations (0/5,P= 0.005). Excessive freckle, a common feature of WS2 in Chinese Hans, was frequent in WS2 probands withMITFmutations (7/10) but not in those withSOX10mutations (0/13,P= 4.9 × 10−4). Our results showed that mutations inSOX10andMITFare two major causes for deafness associated with WS2. These two subtypes of WS2 can be distinguished by the highde novorate of theSOX10mutations and the excessive freckle phenotype exclusively associated with theMITFmutations.
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影响因子：
64.5
作者：
PUFFENBERGER, EG;HOSODA, K;CHAKRAVARTI, A
通讯作者：
CHAKRAVARTI, A
影响因子：
64.5
作者：
HODGKINSON, CA;MOORE, KJ;ARNHEITER, H
通讯作者：
ARNHEITER, H
影响因子：
4
作者：
Read, AP;Newton, VE
通讯作者：
Newton, VE
影响因子：
5.3
作者：
Selicorni, A;Guerneri, S;Pizzuti, A
通讯作者：
Pizzuti, A
DOI：
10.1159/000322471
发表时间：
2011-01-01
期刊：
MEDICAL GENETICS IN THE CLINICAL PRACTICE OF ORL
影响因子：
--
作者：
Toriello, Helga V.
通讯作者：
Toriello, Helga V.