Clinical Exome Sequencing Identifies a Frameshift Mutation Within the STRC Gene in a United Arab Emirates Family with Profound Nonsyndromic Hearing Loss

Genet Test Mol Biomarkers. 2019 Mar;23(3):204-208. doi: 10.1089/gtmb.2018.0264. Epub 2019 Feb 13.

Abstract

Aims: Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of hereditary deafness. Despite its frequency, the diagnosis of this disorder continues to be a challenging task given its extreme genetic heterogeneity. The purpose of this study was to identify the causative mutation in a consanguineous United Arab Emirates (UAE) family with ARNSHL.

Materials and methods: Clinical exome sequencing (CES) followed by segregation analysis via Sanger sequencing was used to identify the causative mutation. In addition, 109 deaf individuals and 50 deafness-free controls from the UAE population were screened for the identified mutation.

Results and discussion: CES identified the STRC frameshift mutation c.4510del (p.Glu1504Argfs*32) as the causative mutation in this family. Moreover, segregation analysis confirmed the above finding. In addition, the absence of this variant in 109 unrelated deaf individuals and 50 healthy controls indicates that it is rare in the UAE population.

Conclusion: The present study represents the first STRC mutation reported in the UAE population. It also reinforces the power of next-generation sequencing in the diagnosis of heterogenous disorders such as nonsyndromic hearing loss.

Keywords: gene; clinical exome sequencing; frameshift mutation; nonsyndromic hearing loss.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Deafness / genetics*
  • Exome / genetics
  • Exome Sequencing
  • Female
  • Frameshift Mutation / genetics
  • Genes, Recessive / genetics
  • Hearing Loss, Sensorineural / genetics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mutation
  • Pedigree
  • United Arab Emirates

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • STRC protein, human

Supplementary concepts

  • Nonsyndromic Deafness