Exome sequencing identifies a novel missense mutation of WFS1 as the cause of non-syndromic low-frequency hearing loss in a Chinese family

Zhijie Niu, Yong Feng, Zhengmao Hu, Jiada Li, Jie Sun, Hongsheng Chen, Chufeng He, Xueping Wang, Lu Jiang, Yalan Liu, Xinzhang Cai, Lili Wang, Yuxiang Cai, Xue Z Liu, Lingyun Mei

Research output: Contribution to journalArticle

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Objective Autosomal dominant non-syndromic low-frequency sensorineural hearing loss (LFSNHL) DFNA6/14/38 is an uncommon type of hearing loss that classically affects low frequencies of 2000 Hz and below, demonstrating an ascending configuration. The current study aimed to investigate the cause of LFSNHL in a five-generation Chinese family. Methods The phenotype of the Chinese family was characterized using audiologic testing and pedigree analysis. The combined approach of array screening and whole-exome sequencing was used to identify the disease-causing gene in this family. Results This pedigree, in which the affected subjects presented isolated low-frequency sensorineural hearing impairment with childhood onset, was associated with autosomal dominant inheritance of the c.2591A > G mutation in exon 8 of the Wolframin syndrome 1 (WFS1) gene which was not present in 286 unrelated controls with matched ancestry and is highly conserved across species. In addition, several mutations affecting the Glu864 residue have been previously identified in different populations, suggesting that this site is likely to be a mutational hot spot. Conclusions We identified a novel substitution, Glu864Gly, of WFS1 as the causative variant for this pedigree. Our data extend the mutation spectrum of the WFS1 gene in Chinese individuals and may contribute to establishing a better genotype-phenotype correlation for LFSNHL.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalInternational Journal of Pediatric Otorhinolaryngology
StatePublished - Sep 1 2017



  • DFNA6/14/38
  • Exome sequencing
  • Low-frequency hearing loss
  • Novel mutation
  • WFS1

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Otorhinolaryngology

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