Identification of novel MITF mutations in Chinese families with Waardenburg syndrome type II

被引:3
作者
Wang, Jing [1 ]
Lu, Yu [2 ]
Yan, Xiaohong [1 ]
Shen, Tian [1 ]
Li, Linke [1 ]
Rao, Yufang [1 ]
Tan, Bo [2 ]
Xiong, Wenyu [2 ]
Cheng, Jing [2 ]
Zhao, Yu [1 ]
Yuan, Huijun [3 ]
机构
[1] Sichuan Univ, West China Hosp, West China Med Sch, Dept Otorhinolaryngol, 37 Guoxue Alley, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, West China Hosp, Inst Rare Dis, Chengdu 610041, Peoples R China
[3] Army Med Univ, Southwest Hosp, Med Genet Ctr, Chongqing, Peoples R China
来源
MOLECULAR GENETICS & GENOMIC MEDICINE | 2021年 / 9卷 / 09期
关键词
incomplete penetrance; MITF; sensorineural hearing loss; Waardenburg syndrome; SOX10; MICROPHTHALMIA; MELANOCYTES; GUIDELINES; ALBINISM; GENES; PAX3;
D O I
10.1002/mgg3.1770
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background Waardenburg syndrome (WS) is a rare autosomal-dominant syndrome and is characterized by sensorineural hearing loss and pigment abnormalities. It is subdivided into four types according to the clinical characteristics. MITF is one of the major pathogenic genes for type II. The aim of this study was to investigate MITF mutations and the clinical characteristics of WS type 2 (WS2) in four Chinese families. Method Clinical diagnoses were based on detailed clinical findings. Six WS2 patients from four unrelated Chinese families were enrolled. Massively parallel DNA sequencing was used to find pathogenic genes and Sanger sequencing was used to confirm the variants detected. Results Sensorineural hearing loss was observed in four of six patients, three had heterochromia iridis, and five have freckled faces. We identified three novel MITF heterozygous mutations (c.831dupC, c.650G>A, and c.711-2A>G) and one recurrent heterozygous mutation (c.328C>T) in the four WS2 families. Intra-familial phenotypic variability and incomplete penetrance were found in WS2 patients with pathogenic variants of MITF. Conclusion Genetic diagnosis was performed for the involved four families based on the clinical manifestations. Four heterozygous mutations were identified in the MITF gene. Our findings expanded the phenotypic and genotypic spectrum of WS.
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页数:7
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