title: A novel missense mutation p.L76P in the GJB2 gene causing nonsyndromic recessive deafness in a Brazilian family.
abstract: Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of nonsyndromic recessive hearing loss in many countries. We report here on a novel point mutation in GJB2, p.L76P (c.227C>T), in compound heterozygosity with a c.35delG mutation, in two Brazilian sibs, one presenting mild and the other profound nonsyndromic neurosensorial hearing impairment. Their father, who carried a wild-type allele and a p.L76P mutation, had normal hearing. The mutation leads to the substitution of leucine (L) by proline (P) at residue 76, an evolutionarily conserved position in Cx26 as well as in other connexins. This mutation is predicted to affect the first extracellular domain (EC1) or the second transmembrane domain (TM2). EC1 is important for connexon-connexon interaction and for the control of channel voltage gating. The segregation of the c.227C>T (p.L76P) mutation together with c.35delG in this family indicates a recessive mode of inheritance. The association between the p.L76P mutation and hearing impairment is further supported by its absence in a normal hearing control group of 100 individuals, 50 European-Brazilians and 50 African-Brazilians.
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Centro de Estudos do Genoma Humano, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: A C
authors.initials: AC
authors.lastname: Batissoco
authors.forename: M T B M
authors.initials: MT
authors.lastname: Auricchio
authors.forename: L
authors.initials: L
authors.lastname: Kimura
authors.forename: A
authors.initials: A
authors.lastname: Tabith-Junior
authors.forename: R C
authors.initials: RC
authors.lastname: Mingroni-Netto
mesh_terms: D001938:Brazil; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000208:ethnology / Q000235:genetics*; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26