Novel compound heterozygous mutations in MYO7A gene associated with autosomal recessive sensorineural hearing loss in a Chinese family

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• 作者：Yalin Ma^a ; ^b ; ^c ; ¹ ; Yun Xiao^a ; ^b ; ¹ ; Fengguo Zhang^a ; ^b ; Yuechen Han^a ; ^b ; Jianfeng Li^a ; ^b ; Lei Xu^a ; ^b ; ^{sdphxl@126.com" class="auth_mail" title="E-mail the corresponding author} ; Xiaohui Bai^a ; ^b ; ^{sphbaixiaohui@163.com" class="auth_mail" title="E-mail the corresponding author} ; Haibo Wang^a ; ^b ; ^{wang.hb7585@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Deafness ; Autosomal recessive inheritance ; MYO7A gene ; Mutation
• 刊名：International Journal of Pediatric Otorhinolaryngology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：179-185
• 全文大小：2155 K

文摘

Mutations in MYO7A gene have been reported to be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Most mutations in MYO7A gene caused USH1B, whereas only a few reported mutations led to DFNB2 and DFNA11. The current study was designed to investigate the mutations among a Chinese family with autosomal recessive hearing loss.

Methods

In this study, we present the clinical, genetic and molecular characteristics of a Chinese family. Targeted capture of 127 known deafness genes and next-generation sequencing were employed to study the genetic causes of two siblings in the Chinese family. Sanger sequencing was employed to examine those variant mutations in the members of this family and other ethnicity-matched controls.

Results

We identified the novel compound heterozygous mutant alleles of MYO7A gene: a novel missense mutation c.3671C > A (p.A1224D) and a reported insert mutation c.390_391insC (p.P131PfsX9). Variants were further confirmed by Sanger sequencing. These two compound heterozygous variants were co-segregated with autosomal recessive hearing loss phenotype. The gene mutation analysis and protein sequence alignment further supported that the novel compound heterozygous mutations were pathogenic.

Conclusion

The novel compound heterozygous mutations (c.3671C > A and c.390_391insC) in MYO7A gene identified in this study were responsible for the autosomal recessive sensorineural hearing loss of this Chinese family.