title: Identification of four novel connexin 26 mutations in non-syndromic deaf patients: genotype-phenotype analysis in moderate cases.
abstract: This paper presents a mutation as well as a genotype-phenotype analysis of the GJB2 and GJB6 genes in 476 samples from non-syndromic unrelated Argentinean deaf patients (104 familial and 372 sporadic cases). Most of them were of prelingual onset (82 %) and 27 % were cochlear implanted. Variation of sequences was detected in 171 of the 474 patients (36 %). Overall, 43 different sequence variations were identified in GJB2 and GJB6. Four of them are reported for the first time in GJB2: c.233dupG, p.Ala78Ser, p.Val190Asp and p.Cys211Tyr. Mutations in GJB6 were detected in 3 % of patients [nine del(GJB6-D13S1830) and three del(GJB6-D13S1854)]. Of the 43 different variations identified in GJB2, 6 were polymorphisms and of the others, 10 (27 %) were truncating and 27 (73 %) were nontruncating. Patients with two truncating mutations had significantly worse hearing impairment than all other groups. Moderate phenotypes were observed in a group of patients carrying biallelic mutations (23 %). This work shows the high prevalence of GJB2 mutations in the Argentinean population and presents an analysis of moderate phenotypes in our cohort.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Dr. Héctor N. Torres (INGEBI) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina, vividalamon@gmail.com.
authors.forename: Viviana
authors.initials: V
authors.lastname: Dalamón
authors.forename: M
authors.initials: M
authors.lastname: Florencia Wernert
authors.forename: Vanesa
authors.initials: V
authors.lastname: Lotersztein
authors.forename: Patricio O
authors.initials: PO
authors.lastname: Craig
authors.forename: Raúl Reynoso
authors.initials: RR
authors.lastname: Diamante
authors.forename: María E
authors.initials: ME
authors.lastname: Barteik
authors.forename: Carlos
authors.initials: C
authors.lastname: Curet
authors.forename: Bibiana
authors.initials: B
authors.lastname: Paoli
authors.forename: Enrique
authors.initials: E
authors.lastname: Mansilla
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Elgoyhen
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001299:Audiometry; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26