title: Novel OTOF mutations in Brazilian patients with auditory neuropathy.
abstract: The OTOF gene encoding otoferlin is associated with auditory neuropathy (AN), a type of non-syndromic deafness. We investigated the contribution of OTOF mutations to AN and to non-syndromic recessive deafness in Brazil. A test for the Q829X mutation was carried out on a sample of 342 unrelated individuals with non-syndromic hearing loss, but none presented this mutation. We selected 48 cases suggestive of autosomal recessive inheritance, plus four familial and seven isolated cases of AN, for genotyping of five microsatellite markers linked to the OTOF gene. The haplotype analysis showed compatibility with linkage in 11 families (including the four families with AN). Samples of the 11 probands from these families and from seven isolated cases of AN were selected for an exon-by-exon screening for mutations in the OTOF gene. Ten different pathogenic variants were detected, among which six are novel. Among the 52 pedigrees with autosomal recessive inheritance (including four familial cases of AN), mutations were identified in 4 (7.7%). Among the 11 probands with AN, seven had at least one pathogenic mutation in the OTOF gene. Mutations in the OTOF gene are frequent causes of AN in Brazil and our results confirm that they are spread worldwide.
authors.affiliation: Departamento de Genética e Biologia Evolutiva, Centro de Estudos do Genoma Humano, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Jihane
authors.initials: J
authors.lastname: Romanos
authors.forename: Lilian
authors.initials: L
authors.lastname: Kimura
authors.forename: Mariana Lopes
authors.initials: ML
authors.lastname: Fávero
authors.forename: Fernanda Attanasio R
authors.initials: FA
authors.lastname: Izarra
authors.forename: Maria Teresa Balester
authors.initials: MT
authors.lastname: de Mello Auricchio
authors.forename: Ana Carla
authors.initials: AC
authors.lastname: Batissoco
authors.forename: Karina
authors.initials: K
authors.lastname: Lezirovitz
authors.forename: Ronaldo Serafim
authors.initials: RS
authors.lastname: Abreu-Silva
authors.forename: Regina Célia
authors.initials: RC
authors.lastname: Mingroni-Netto
mesh_terms: D001938:Brazil; D016022:Case-Control Studies; D003638:Deafness / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C118457:OTOF protein, human