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Author Notes:

Corresponding author: Pu Dai, PhD and Xi Lin, PhD, daipu301@vip.sina.com and xlin2@emory.edu.

Xue Gao and Sha-Sha Huang are listed as co-first authors.

XG, SSH, PD, XL conceived of the study and participated in its design and draft the manuscript.

YYY participated in the next generation sequencing.

JCX, YBJ, YL participated in the data analysis.

GJW, MYH, FY, DYK participated in the collection of clinical data and blood samples.

We sincerely thank all the family members for their participation and cooperation in this study. We are also grateful to Dr. Guangchun Bai of Albany Medical College, New York State Department of Health for his valuable comments and suggestions.

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Research Funding:

This work was supported by grants from the Project of the National Natural Science Foundation of China (Grant Nos. 30801285, 81230020, 81200751, 81000415, 81371098, 81371096, 81400471, 81371352), grants from China Postdoctoral Science Foundation (2012M521878, 2013T60947), a grant from Military Twelfth Five-year Project of China (CWS115034), a grant from Minister of Science and Technology of China (2012BAI09B02), grants from the National Basic Research Program of China (973 Program) (2014CB541706, 2014CB541701) and a grant from Minister of Health of China (201202005).

Work performed in the Lin lab was supported by a grant from NIH (R33 DC010476).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • autosomal dominant nonsyndromic hearing loss
  • targeted gene capture
  • massively parallel sequencing
  • TMC1
  • HAIR-CELL-FUNCTION
  • INNER-EAR
  • MUTATIONS
  • DEAFNESS
  • CHANNEL
  • IMPAIRMENT
  • PROTEIN
  • DFNA36
  • MOUSE
  • MECHANOTRANSDUCTION
  • Otolaryngology

Targeted gene capture and massively parallel sequencing identify TMC1 as the causative gene in a six-generation Chinese family with autosomal dominant hearing loss

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Journal Title:

American Journal of Medical Genetics Part A

Volume:

Volume 167, Number 10

Publisher:

, Pages 2357-2365

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the transmembrane channel-like gene1 (TMC1) are known to cause autosomal dominant and recessive forms of nonsyndromic hearing loss linked to the loci of DFNA36 and DFNB7/11, respectively. We characterized a six-generation Chinese family (5315) with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 82 known deafness genes, next-generation sequencing and bioinformatic analysis, we identified TMC1 c.1714G>A (p. D572N) as the disease-causing mutation. This mutation co-segregated with hearing loss in other family members and was not detected in 308 normal controls. In order to determine the prevalence of TMC1 c.1714G>A in Chinese ADNSHL families, we used DNA samples from 67 ADNSHL families with sloping audiogram and identified two families carry this mutation. To determine whether it arose from a common ancestor, we analyzed nine STR markers. Our results indicated that TMC1 c.1714G>A (p.D572N) account for about 4.4% (3/68) of ADNSHL in the Chinese population.

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© 2015 Wiley Periodicals, Inc.

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