title: Cx26 gene mutations in idiopathic progressive hearing loss.
abstract: OBJECTIVE
  The present study evaluated the frequency and type of mutations throughout the entire GJB2 region in a population of 39 patients affected with sporadic progressive "idiopathic" hearing loss.
  
  
  METHODS
  A large series of patients suffering from progressive hearing loss underwent a systematic screening program to identify the etiology of the hearing loss. Of these patients, 39 presented with sporadic idiopathic progressive hearing loss and were included in this study.
  
  
  METHODS
  We performed molecular analysis of GJB2 in each patient sequencing the genomic deoxyribonucleic acid (DNA) in both directions for detection of GJB2 mutations. Furthermore, in all patients bearing a Cx26 mutation, a search was also conducted for mutations or deletions of GJB6 (Cx30 gene) and for the A1555G mutation of the mitochondrial DNA. A control group was also considered to evaluate the frequency of Cx26 mutations in the normal population.
  
  
  RESULTS
  A Cx26 gene mutation was detected in nine cases. One subject was found to bear a homozygous genotype for the 35delG mutation, another subject was compound heterozygous for 35delG and E47X, and the remaining patients showed heterozygous genotypes (35delG, L90P, R127H, M34T, V153I, V37I). No mutation or delection of the Cx30 gene was observed in these nine patients, and none of them presented with the A1555G mutation in the mitochondrial DNA. In the control group (40 individuals), a Cx26 mutation was detected in two cases (5%).
  
  
  CONCLUSIONS
  About 23% of our patients (nine subjects) presented with mutations in GJB2, and 18% (seven subjects) were heterozygous. However, most of the described mutations are recessive, so a monogenic model of inheritance cannot explain the deafness phenotype. On the basis of these findings, we can speculate that the heterozygote Cx26 genotype could be a cause of progressive hearing loss, probably in association with mutations in other alleles. Thus, we recommend carefully following all hearing-impaired subjects with GJB2 mutations, even if they present with only mild hearing loss, because the hearing deficit could worsen. Furthermore, molecular analysis of the Cx26 gene should also be performed in adult patients affected with idiopathic progressive hearing loss.
authors.affiliation: Neuroscience Department, University of Pisa, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ravecca
authors.forename: Stefano
authors.initials: S
authors.lastname: Berrettini
authors.forename: Francesca
authors.initials: F
authors.lastname: Forli
authors.forename: Mirella
authors.initials: M
authors.lastname: Marcaccini
authors.forename: Augusto
authors.initials: A
authors.lastname: Casani
authors.forename: Fulvia
authors.initials: F
authors.lastname: Baldinotti
authors.forename: Antonella
authors.initials: A
authors.lastname: Fogli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Paolo
authors.initials: P
authors.lastname: Simi
mesh_terms: D000328:Adult; D001774:Blood Chemical Analysis; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D018450:Disease Progression; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D000072259:Connexin 26