title: Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling.
abstract: OBJECTIVE
  To evaluate difficulties encountered in genetic counseling in deaf children carrying connexin 26 gene (CX26 or GJB2) mutations.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Outpatients, tertiary referral center.
  
  
  METHODS
  Ninety-six unrelated deaf children in whom CX26 mutations had been detected consecutively. Children were recruited to a center for genetic counseling for deaf children, and all had congenital deafness, sporadic or familial.
  
  
  RESULTS
  In 63 children, deafness was clearly a DFNB1 form with autosomal recessive inheritance: 47 of the 63 were homozygous for the most frequent mutation, the deletion of G at position 35 (35delG); 16 of 63 carried on both alleles of CX26 frameshift or stop mutations, or missense mutations affecting a critical region of the gene. In 33 of 96 children, genetic counseling was difficult: 21 of 33 had a single mutation detected, 11 of 33 had new missense mutations or mutations whose pathogenicity remains debated in the literature, and 1 of 33 had a genotype with both a recessive mutation (35delG) and a mutation acting as a dominant mutation.
  
  
  CONCLUSIONS
  Interpretation of results for the molecular diagnosis of mutations in the connexin 26 gene is difficult in almost one third of cases. Close collaboration between geneticists familiar with deafness and otolaryngologists is essential to provide a high standard of genetic advice.
authors.affiliation: Service d'ORL Pédiatrique et de Chirurgie Cervicofaciale, Hôpital d'Enfants Armand-Trousseau, and Université Paris VI, Paris CEDEX 05, France.
authors.forename: S
authors.initials: S
authors.lastname: Marlin
authors.forename: E N
authors.initials: EN
authors.lastname: Garabédian
authors.forename: G
authors.initials: G
authors.lastname: Roger
authors.forename: L
authors.initials: L
authors.lastname: Moatti
authors.forename: N
authors.initials: N
authors.lastname: Matha
authors.forename: P
authors.initials: P
authors.lastname: Lewin
authors.forename: C
authors.initials: C
authors.lastname: Petit
authors.forename: F
authors.initials: F
authors.lastname: Denoyelle
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000151:congenital / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005817:Genetic Counseling; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D022821:RNA Splice Sites; D000072259:Connexin 26