title: Prevalence of DFNB1 mutations in Argentinean children with non-syndromic deafness. Report of a novel mutation in GJB2.
abstract: OBJECTIVE
  Mutations in DFNB1 locus, containing GJB2 (connexin 26) and GJB6 (connexin 30) genes, are the most common cause of autosomal recessive non-syndromic hearing loss. More than 100 mutations in GJB2 have been reported worldwide. Two deletions in GJB6, del(GJB6-D13S1830) and del(GJB6-D13S1854), have been found to be frequent in the Spanish population. The aim of this study was to determine the prevalence of GJB2 mutations and both GJB6 deletions in Argentinean children with non-syndromic deafness.
  
  
  METHODS
  This study included 94 unrelated children with moderate to profound non-syndromic sensorineural hearing impairment. Molecular analysis was performed using a tiered approach. All DNA samples were screened for c.35delG mutation by PCR/RFLP. Samples from patients who were not homozygous for c.35delG were analysed for the presence of GJB6 deletions by PCR multiplex. The samples that remained unresolved after screening were further analysed by direct sequencing of GJB2 coding region. Finally, the splice site mutation IVS1+1G-->A was analysed by PCR/RFLP.
  
  
  RESULTS
  Sequence variations in the GJB2 and GJB6 genes were found in 49 of the 94 unrelated patients. The most prevalent GJB2 mutation, c.35delG, was found in 40 of the 68 pathogenic alleles with the second most common allele being p.R143W (4/68). Fourteen sequence variations other than c.35delG were identified. Seven already described mutations were present in more than one allele; among them, IVS1+1G-->A, the rare splice site mutation flanking exon 1. In addition to known disease-related alterations, a novel GJB2 mutation, c.262G>C (p.A88P), was also identified. Six alleles were identified carrying GJB6 deletions; the most prevalent was del(GJB6-D13S1830). The frequency of the latter was found to be as high as that found in Spain from where Argentina has received one of its major immigration waves.
  
  
  CONCLUSIONS
  The overall frequency of GJB2/GJB6 mutations in the present sample is in agreement with other Caucasian populations. As expected, c.35delG was the most prevalent mutation. The deletion del(GJB6-D13S1830) was the second most common mutation. These findings reinforce the importance of the study of GJB2/GJB6 genes in diagnosis to provide early treatment and genetic counselling.
authors.affiliation: Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Combate de los Pozos 1881, 1245 Buenos Aires, Argentina.
authors.forename: Luis Pablo
authors.initials: LP
authors.lastname: Gravina
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Foncuberta
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Prieto
authors.forename: Jeniffer
authors.initials: J
authors.lastname: Garrido
authors.forename: Cristina
authors.initials: C
authors.lastname: Barreiro
authors.forename: Lilien
authors.initials: L
authors.lastname: Chertkoff
mesh_terms: D000293:Adolescent; D001118:Argentina / Q000453:epidemiology; D001301:Audiometry, Pure-Tone; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant / Q000235:genetics; D003638:Deafness / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016678:Genome; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation / Q000235:genetics*
chemical_list: D017630:Connexins; D004274:DNA, Recombinant; C000607042:GJB2 protein, human; D000072259:Connexin 26