title: Compound heterozygosity for dominant and recessive GJB2 mutations in a Tunisian family and association with successful cochlear implant outcome.
abstract: OBJECTIVE
  Mutations of GJB2 encoding connexin 26 are the most common cause of hearing loss. They are responsible for up to 50% of ARNSHL. The pathogenic mutations in this gene are generally inherited recessively. Dominant mutations in GJB2 also cause hearing loss, either in isolated non-syndromic form or as part of a syndrome associated with various skin disorders.
  
  
  METHODS
  We screened a Tunisian child affected by congenital, bilateral, profound, sensorineural hearing loss for mutations in GJB2 gene using PCR and direct sequencing.
  
  
  RESULTS
  The proband was found to be compound heterozygous for recessive and dominant GJB2 mutations respectively p.V37I (c.109G > A) and p.R143Q (c.428G > A). Surprisingly the hearing mother is a carrier for this dominant GJB2 mutation. This proband underwent a cochlear implant at four years old. The evaluation using APCEI and IT-MAIS tests at six months post implantation indicates a successful cochlear implant outcome since the deaf child began to acquire language abilities and auditory sensation.
  
  
  CONCLUSIONS
  The p.R143Q mutation was described for the first time in Tunisia. We confirm the low penetrance of this mutation since the proband mother is a carrier despite her normal hearing. We show the effectiveness of cochlear implant to restore the communication abilities and auditory sensation for our patient.
authors.affiliation: Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, Tunis 1002, Tunisia.
authors.forename: Zied
authors.initials: Z
authors.lastname: Riahi
authors.forename: Rim
authors.initials: R
authors.lastname: Zainine
authors.forename: Yosra
authors.initials: Y
authors.lastname: Mellouli
authors.forename: Raja
authors.initials: R
authors.lastname: Hannachi
authors.forename: Yosra
authors.initials: Y
authors.lastname: Bouyacoub
authors.forename: Nadia
authors.initials: N
authors.lastname: Laroussi
authors.forename: Najeh
authors.initials: N
authors.lastname: Beltaief
authors.forename: Rym
authors.initials: R
authors.lastname: Kefi
authors.forename: Lilia
authors.initials: L
authors.lastname: Romdhane
authors.forename: Crystel
authors.initials: C
authors.lastname: Bonnet
authors.forename: Sonia
authors.initials: S
authors.lastname: Abdelhak
authors.forename: Ghazi
authors.initials: G
authors.lastname: Besbes
mesh_terms: D001299:Audiometry; D002675:Child, Preschool; D019929:Cochlear Implantation / Q000379:methods*; D003054:Cochlear Implants; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics* / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening / Q000379:methods; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D006579:Heterozygote; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D014416:Tunisia
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: Cochlear implant; Dominant; GJB2; Hearing loss; Penetrance; Tunisia