Mutation spectra and founder effect of TMC1 in patients with non-syndromic deafness in Xiamen area, China

作者：Jiang, Yi; Gao, Song; Wu, Lihua; Jin, Xiaohua; Deng, Tao; Wang, Ligang; Huang, Shasha; Gao, Xue; Chen, Juan; Han, Dongyi^*; Gao, Huafang^*; Dai, Pu^*

来源：American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 2018, 177(3): 301-307.

DOI：10.1002/ajmg.b.32603

• founder effect
• haplotype
• hearing impairment
• single nucleotide polymorphisms

To analyze the spectrum and founder effect of TMC1 mutations in patients with non-syndromic deafness in the Xiamen area. Sporadic pedigrees were detected by targeted next-generation sequencing, and 110 unrelated patients from Xiamen Special Education School were analyzed through Sanger sequencing for the TMC1 gene. In total, 53 SNPs were designed to analyze the haplotypes of the TMC1 c.2050G>C mutation. The probands of three families were found to be homozygous for TMC1 c.2050G>C, and their parents were all heterozygous for the TMC1 c.2050G>C mutation. In 110 unrelated patients from Xiamen Special Education School, four were found to carry compound heterozygotes of TMC1 c.2050G>C, which were compound heterozygotes of c.804G>A, c.1127T>C, c.1165C>T, and c.1396_1398delAAC, respectively. Three types of TMC1 polymorphisms (c.45C>T, c.1713C>T, c.2208+49C>T) and two heterozygotes of novel variants (c.1764-4C>A, c.2073G>A[p.K691K]) were found in the remaining 100 patients. In total, four novel variants were detected in this study. These mutations and variants were not detected in 100 normal samples. The haplotypes of the probands of families with TMC1 c.2050G>C were identical. There were unique hotspots and spectra of TMC1 mutations in the Xiamen deaf population. Haplotype analysis is useful to understand the founder effect of the hot spot mutation.

• 出版日期2018-4
• 单位中国人民解放军总医院; 福建省立医院; 福建医科大学; 厦门大学; 国家卫生计生委科学技术研究所