title: Identification of a novel frameshift mutation in the DFNB31/WHRN gene in a Tunisian consanguineous family with hereditary non-syndromic recessive hearing loss.
abstract: Approximately 80% of hereditary hearing loss is non-syndromic. Non-syndromic deafness is the most genetically heterogeneous trait. The most common and severe form of hereditary hearing impairment is autosomal recessive non-syndromic hearing loss (ARNSHL), accounting for approximately 80% of cases of genetic deafness. To date, 22 genes implicated in ARNSHL have been identified. Recently a gene, DFNB31/WHRN, which encodes a putative PDZ scaffold protein called whirlin, was found to be responsible for the ARNSHL DFNB31. We found evidence for linkage to the DFNB31locus in a consanguineous Tunisian family segregating congenital profound ARNSHL. Mutation screening of DFNB31/WHRNrevealed four nonpathogenic sequence variants and a novel frameshift mutation [c.2423delG] + [c.2423delG] that changed the reading frame and induced a novel stop codon at amino acid 818 ([p.Gly808AspfsX11] + [p.Gly808AspfsX11]). To determine the contribution of the DFNB31locus in the childhood deafness, we performed linkage analysis in 62 unrelated informative families affected with ARNSHL. No linkage was found to this locus. From this study, we concluded that DFNB31/WHRN is most likely to be a rare cause of ARNSHL in the Tunisian population.
authors.affiliation: Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Sfax, Tunisia.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Tlili
authors.forename: Ilhem
authors.initials: I
authors.lastname: Charfedine
authors.forename: Imed
authors.initials: I
authors.lastname: Lahmar
authors.forename: Zaineb
authors.initials: Z
authors.lastname: Benzina
authors.forename: Ben Amor
authors.initials: BA
authors.lastname: Mohamed
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: Nabil
authors.initials: N
authors.lastname: Idriss
authors.forename: Mohamed
authors.initials: M
authors.lastname: Drira
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
mesh_terms: D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D006239:Haplotypes; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D014416:Tunisia / Q000208:ethnology
chemical_list: D008565:Membrane Proteins; C477219:WHRN protein, human