title: DFNB1-associated deafness in Portuguese cochlear implant users: prevalence and impact on oral outcome.
abstract: OBJECTIVE
  Hearing loss is a condition that interferes with the development of the child at a cognitive and language level. Therefore, early diagnosis of deafness is important for (re)habilitation, namely through the use of cochlear implant (CI). The present study aimed at screening CI Portuguese individuals for the presence of mutations in the genes GJB2 and GJB6 (DFNB1 locus), and searching a possible correlation between the genotype and the oral habilitation outcome following implantation.
  
  
  METHODS
  Our sample included 117 CI individuals implanted longer than 5 years. Sequencing of GJB2 entire coding region was first performed. The presence of deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) was subsequently tested by multiplex PCR. To assess the oral outcome of these individuals, a global score is calculated through a formula that integrates the results of a battery of speech and audiological tests routinely used in ORL services. This global oral performance score was used to test whether individuals with DFNB1-associated deafness perform significantly better than individuals without DFNB1-associated deafness.
  
  
  RESULTS
  In 35% of the cases, deafness was clearly associated to DFNB1. The most common mutated allele was c.35delG (85%). Other variants have also been found, namely p.Gly130Ala, p.Asn206Ser, p.Val37Ile, p.Glu47X, p.Arg184Trp, p.Trp24X and the two common GJB6 deletions, del(GJB6-D13S1854) and del(GJB6-D13S1830), the last one identified for the first time in our population. Regarding the oral outcome, after testing the homogeneity of the two groups it could be observed that, in mean, the individuals with DFNB1-associated deafness perform significantly better (p=0.012) than the individuals without DFNB1-associated deafness.
  
  
  CONCLUSIONS
  This first screening of DFNB1 genes in the Portuguese CI population provides clear evidence of the high proportion of DFNB1-associated deafness amongst the Portuguese implanted individuals. DFNB1 status is significantly associated to higher oral performance scores, with DFNB1 individuals performing, on average, 6% better than the individuals without DFNB1-associated deafness.
authors.affiliation: BioFIG, Center for Biodiversity, Functional and Integrative Genomics, University of Lisbon, C2, Faculty of Science of the University of Lisbon Campus, 1749-016 Lisbon, Portugal.
authors.forename: Joana Rita Gaspar de Barros Martinho
authors.initials: JR
authors.lastname: Chora
authors.forename: Tiago Daniel Morim
authors.initials: TD
authors.lastname: Matos
authors.forename: Jorge Humberto Ferreira
authors.initials: JH
authors.lastname: Martins
authors.forename: Marisa Costa
authors.initials: MC
authors.lastname: Alves
authors.forename: Susana Margarida Sousa
authors.initials: SM
authors.lastname: Andrade
authors.forename: Luis Filipe dos Santos
authors.initials: LF
authors.lastname: Silva
authors.forename: Carlos Alberto dos Reis
authors.initials: CA
authors.lastname: Ribeiro
authors.forename: Marília Cristina de Sousa
authors.initials: MC
authors.lastname: Antunes
authors.forename: Maria Graça Monteiro Azevedo
authors.initials: MG
authors.lastname: Fialho
authors.forename: Maria Helena de Figueiredo Ramos
authors.initials: MH
authors.lastname: Caria
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019929:Cochlear Implantation; D003054:Cochlear Implants; D015331:Cohort Studies; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics* / Q000628:therapy; D005260:Female; D006801:Humans; D007223:Infant; D007804:Language Development; D008297:Male; D009154:Mutation; D011174:Portugal; D015995:Prevalence; D013065:Speech Intelligibility; D013067:Speech Perception
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26