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A novel p.Leu213X mutation in GJB2 gene in a Portuguese family

Ana Cláudia Gonçalves1, Joana Chora, Tiago D Matos

  • 1BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Faculty of Science of the University of Lisbon, Portugal.

International Journal of Pediatric Otorhinolaryngology
|November 13, 2012
PubMed

Insights

Genetic analysis identified a novel GJB2 mutation (p.Leu213X) causing hearing loss in two Portuguese siblings. This nonsense mutation, combined with a known deletion, explains their nonsyndromic sensorineural deafness.

Area of Science:

  • Genetics
  • Audiology
  • Molecular Biology

Background:

  • Hearing loss is a prevalent global disability, affecting approximately 1.9 per 1000 newborns.
  • The GJB2 gene, encoding connexin 26, is a key player in the DFNB1 locus and is associated with numerous hearing loss mutations.
  • Over 100 mutations in GJB2 have been linked to both autosomal dominant and recessive forms of hearing loss.

Purpose of the Study:

  • To determine the genetic cause of deafness in two Portuguese individuals with nonsyndromic sensorineural hearing loss.
  • To investigate the role of GJB2 gene mutations in the etiology of hearing impairment.

Main Methods:

  • Pure tone audiometry was performed on both ears of the affected individuals.
  • DNA was extracted from blood samples, and the GJB2 coding region was amplified using PCR.
  • Automated sequencing of PCR products was conducted in both directions to identify mutations.

Main Results:

  • A novel nonsense mutation, c.638T>A (p.Leu213X), was identified in the GJB2 gene of both siblings.
  • This new mutation, which introduces a premature STOP codon and truncates connexin 26, was inherited from their father.
  • The siblings were also found to be compound heterozygous for a previously described GJB2 deletion (c.333-334delAA).
  • The novel p.Leu213X mutation was absent in a control sample of 480 individuals.

Conclusions:

  • The hearing loss in the studied individuals is attributed to compound heterozygosity for the GJB2 c.333-334delAA deletion and the novel p.Leu213X mutation.
  • This genetic finding elucidates the etiology of nonsyndromic sensorineural hearing loss in this family.
Abstract

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