title: Spectrum and frequency of GJB2 mutations in a cohort of 264 Portuguese nonsyndromic sensorineural hearing loss patients.
abstract: OBJECTIVE
  To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients.
  
  
  METHODS
  Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions.
  
  
  METHODS
  A cohort of 264 Portuguese NSSHL patients.
  
  
  RESULTS
  At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations.
  
  
  CONCLUSIONS
  This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families.
authors.affiliation: Centre for Biodiversity, Functional, and Integrative Genomics BioFIG, Faculty of Science, University of Lisbon, Lisboa, Portugal.
authors.forename: Tiago Daniel
authors.initials: TD
authors.lastname: Matos
authors.forename: Helena
authors.initials: H
authors.lastname: Simões-Teixeira
authors.forename: Helena
authors.initials: H
authors.lastname: Caria
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Gonçalves
authors.forename: Joana
authors.initials: J
authors.lastname: Chora
authors.forename: Maria do Céu
authors.initials: Mdo C
authors.lastname: Correia
authors.forename: Carla
authors.initials: C
authors.lastname: Moura
authors.forename: Helena
authors.initials: H
authors.lastname: Rosa
authors.forename: Luísa
authors.initials: L
authors.lastname: Monteiro
authors.forename: Assunção
authors.initials: A
authors.lastname: O'Neill
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Dias
authors.forename: Mário
authors.initials: M
authors.lastname: Andrea
authors.forename: Graça
authors.initials: G
authors.lastname: Fialho
mesh_terms: D001299:Audiometry; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D009154:Mutation; D038781:Otoscopy; D010641:Phenotype; D011174:Portugal; D022821:RNA Splice Sites; D012720:Severity of Illness Index
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D022821:RNA Splice Sites; D000072259:Connexin 26