title: A novel p.Leu213X mutation in GJB2 gene in a Portuguese family.
abstract: BACKGROUND
  Hearing loss is the most common sensory disability and is present in about 1.9 per 1000 infants at birth. The DFNB1 locus (13q11-q12) includes the genes GJB2, coding for connexin 26, and GJB6, encoding connexin 30. More than 100 mutations have been identified associated with autosomal dominant and recessive hearing loss in the GJB2 gene.
  
  
  OBJECTIVE
  The aim of the present study was to identify the genetic aetiology of deafness in two Portuguese individuals, presenting nonsyndromic sensorineural moderate and severe hearing loss, respectively.
  
  
  METHODS
  The individuals were evaluated in both ears by pure tone audiometry and blood samples were collected after written informed consent was signed. DNA extraction and PCR amplification of GJB2 coding region followed standard methodologies. PCR products were automatically sequenced in both directions.
  
  
  RESULTS
  We identified a novel mutation, c.638T>A (p.Leu213X), in GJB2 gene. This nonsense mutation was found in both siblings, and was inherited from their hearing father. Molecular analysis showed that the two siblings were also heterozygous for c.333-334delAA, a previously described GJB2 deletion. This novel mutation was not found in a random control sample of 480 individuals that were screened for coding region of GJB2 gene. p.Leu213X mutation identified in this study for the first time changes the codon 213, coding for a highly conserved and slowly evolving residue of connexin 26, localised to the C-terminus domain of the protein, to a STOP codon, leading to the deletion of the last 14 amino acids of the protein.
  
  
  CONCLUSIONS
  We can conclude that the aetiology of deafness in these individuals is due to the GJB2 genotype involving the c.333-334delAA deletion and the novel p.Leu213X mutation in compound heterozygosity.
authors.affiliation: BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Faculty of Science of the University of Lisbon, Portugal.
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Gonçalves
authors.forename: Joana
authors.initials: J
authors.lastname: Chora
authors.forename: Tiago D
authors.initials: TD
authors.lastname: Matos
authors.forename: Ricardo
authors.initials: R
authors.lastname: Santos
authors.forename: Assunção
authors.initials: A
authors.lastname: O'Neill
authors.forename: Pedro
authors.initials: P
authors.lastname: Escada
authors.forename: Graça
authors.initials: G
authors.lastname: Fialho
authors.forename: Helena
authors.initials: H
authors.lastname: Caria
mesh_terms: D000293:Adolescent; D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011174:Portugal; D035781:Siblings
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26