PLoS ONE (Jan 2014)

Novel compound heterozygous mutations in MYO7A Associated with Usher syndrome 1 in a Chinese family.

  • Xue Gao,
  • Guo-Jian Wang,
  • Yong-Yi Yuan,
  • Feng Xin,
  • Ming-Yu Han,
  • Jing-Qiao Lu,
  • Hui Zhao,
  • Fei Yu,
  • Jin-Cao Xu,
  • Mei-Guang Zhang,
  • Jiang Dong,
  • Xi Lin,
  • Pu Dai

DOI
https://doi.org/10.1371/journal.pone.0103415
Journal volume & issue
Vol. 9, no. 7
p. e103415

Abstract

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Usher syndrome is an autosomal recessive disease characterized by sensorineural hearing loss, age-dependent retinitis pigmentosa (RP), and occasionally vestibular dysfunction. The most severe form is Usher syndrome type 1 (USH1). Mutations in the MYO7A gene are responsible for USH1 and account for 29-55% of USH1 cases. Here, we characterized a Chinese family (no. 7162) with USH1. Combining the targeted capture of 131 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified two deleterious compound heterozygous mutations in the MYO7A gene: a reported missense mutation c.73G>A (p.G25R) and a novel nonsense mutation c.462C>A (p.C154X). The two compound variants are absent in 219 ethnicity-matched controls, co-segregates with the USH clinical phenotypes, including hearing loss, vestibular dysfunction, and age-dependent penetrance of progressive RP, in family 7162. Therefore, we concluded that the USH1 in this family was caused by compound heterozygous mutations in MYO7A.