title: Assessing Noncoding Sequence Variants of GJB2 for Hearing Loss Association.
abstract: Involvement of GJB2 noncoding regions in hearing loss (HL) has not been extensively investigated. However, three noncoding mutations, c.-259C>T, c.-23G>T, and c.-23+1G>A, were reported. Also, c.-684_-675del, of uncertain pathogenicity, was found upstream of the basal promoter. We performed a detailed analysis of GJB2 noncoding regions in Portuguese HL patients (previously screened for GJB2 coding mutations and the common GJB6 deletions) and in control subjects, by sequencing the basal promoter and flanking upstream region, exon 1, and 3'UTR. All individuals were genotyped for c.-684_-675del and 14 SNPs. Novel variants (c.-731C>T, c.-26G>T, c.*45G>A, and c.*985A>T) were found in controls. A hearing individual homozygous for c.-684_-675del was for the first time identified, supporting the nonpathogenicity of this deletion. Our data indicate linkage disequilibrium (LD) between SNPs rs55704559 (c.*168A>G) and rs5030700 (c.*931C>T) and suggest the association of c.[*168G;*931T] allele with HL. The c.*168A>G change, predicted to alter mRNA folding, might be involved in HL.
authors.affiliation: Centre for Biodiversity, Functional, and Integrative Genomics (BioFIG), Faculty of Science, University of Lisbon, Campus FCUL, Campo Grande, 1749-016 Lisboa, Portugal.
authors.forename: T D
authors.initials: TD
authors.lastname: Matos
authors.forename: H
authors.initials: H
authors.lastname: Simões-Teixeira
authors.forename: H
authors.initials: H
authors.lastname: Caria
authors.forename: R
authors.initials: R
authors.lastname: Cascão
authors.forename: H
authors.initials: H
authors.lastname: Rosa
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.forename: O
authors.initials: O
authors.lastname: Dias
authors.forename: M E
authors.initials: ME
authors.lastname: Andrea
authors.forename: D P
authors.initials: DP
authors.lastname: Kelsell
authors.forename: G
authors.initials: G
authors.lastname: Fialho