Received: 23 June 2017
Revised: 26 August 2017
Accepted: 11 September 2017
Mutation spectra and founder effect of TMC1 in patients with
non-syndromic deafness in Xiamen area, China
Department of Otolaryngology, Head and Neck Surgery, PLA General Hospital, Beijing, P. R. China
Department of Otolaryngology, Fujian Medical University ShengLi Clinical College, Fujian Provincial Hospital, Fuzhou, P.R. China
Department of Otolaryngology, The 175th Hospital of PLA, South-East Hospital Affiliated to Xiamen University, Zhangzhou, P. R. China
National Research Institute for Family Planning, Beijing, P. R. China
National Human Genetic Resources Center, Beijing, P. R. China
Beijing Capital Bio Independent Clinical Laboratory, Beijing, P. R. China
Department of Otolaryngology, PLA Rocket Force General Hospital, Beijing, P. R. China
Dongyi Han and Pu Dai, Department of
Otolaryngology, Head and Neck Surgery, PLA
General Hospital, 28# Fuxing Road, Beijing,
100853, P. R. China.
Email: firstname.lastname@example.org (P.D);
Huafang Gao, National Research Institute for
Family Planning, Beijing, P. R. China.
National Natural Science Foundation of China,
Grant number: 81230020; National Key
Research and Development Program of China,
Grant numbers: 2016YFC1000700,
2016YFC1000704, 2016YFC1000706; Fujian
Provincial Medical Innovation Project,
Grant number: 2016-CX-5
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.
founder effect, haplotype, hearing impairment, single nucleotide polymorphisms
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in
any medium, provided the original work is properly cited and is not used for commercial purposes.
© 2017 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.
Yi Jiang, Song Gao, and Lihua Wu contributed equally to this work.
The English in this document has been checked by two professional editors who are native speakers of English.
Am J Med Genet. 2018;177B:301–307. wileyonlinelibrary.com/journal/ajmgb