title: Screening of the DFNB3 locus: identification of three novel mutations of MYO15A associated with hearing loss and further suggestion for two distinctive genes on this locus.
abstract: Recessive mutations of MYO15A are associated with nonsyndromic hearing loss (HL) in humans (DFNB3) and in the shaker-2 mouse. Human MYO15A has 66 exons and encodes unconventional myosin XVA. Analysis of 77 Tunisian consanguineous families segregating recessive deafness revealed evidence of linkage to microsatellite markers for DFNB3 in four families. In two families, sequencing of MYO15A led to the identification of two novel homozygous mutations: a nonsense (c.4998C>A (p.C1666X) in exon 17 and a splice site mutation in intron 54 (c.9229 + 1G>A). A novel mutation of unknown significance, c.7395 + 3G>C, was identified in the third family, and no mutation was found in the fourth family. In conclusion, we discovered three novel mutations of MYO15A, and our data suggest the possibility that there are two distinct genes at the DFNB3 locus.
authors.affiliation: Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie de Sfax, Sfax, Tunisia.
authors.forename: Hanen
authors.initials: H
authors.lastname: Belguith
authors.forename: Mounira
authors.initials: M
authors.lastname: Aifa-Hmani
authors.forename: Houria
authors.initials: H
authors.lastname: Dhouib
authors.forename: Mariem Ben
authors.initials: MB
authors.lastname: Said
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Mosrati
authors.forename: Imed
authors.initials: I
authors.lastname: Lahmar
authors.forename: Jihen
authors.initials: J
authors.lastname: Moalla
authors.forename: Ilhem
authors.initials: I
authors.lastname: Charfeddine
authors.forename: Nabil
authors.initials: N
authors.lastname: Driss
authors.forename: Saida Ben
authors.initials: SB
authors.lastname: Arab
authors.forename: Abdelmonem
authors.initials: A
authors.lastname: Ghorbel
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
mesh_terms: D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D014416:Tunisia
chemical_list: D018389:Codon, Nonsense; C485245:MYO15A protein, human; D022821:RNA Splice Sites; D009218:Myosins