title: DFNB3, spectrum of MYO15A recessive mutant alleles and an emerging genotype-phenotype correlation.
abstract: We have now identified seven MYO15A mutations that cause congenital profound neurosensory hearing loss and a possible hypomorphic allele of MYO15A associated with moderately-severe hearing loss in 1 of 8 SMS patients. Because myosin XVA is encoded by 66 exons, screening for mutations in hearing-impaired individuals is expensive and labor-intensive in comparison to a screen for mutations in GJB2 (Cx26), for example, which has only a single protein coding exon. Among consanguineous families segregating profound, congenital hearing loss from Pakistan, approximately 10% are consistent with linkage to DFNB3 (11 of 112 DFNB families). In one-half of these DFNB3 families, we found a homozygous mutation in 1 of the 66 exons of MYO15A [25]. This suggests that mutations of MYO15A are responsible for at least 5% of recessively inherited, profound hearing loss in Pakistan. However, without the benefit of a pre-screen for linkage to DFNB3, it will be a challenge to determine the extent to which mutations of MYO15A contribute to hereditary hearing loss among isolated cases and small families in other populations.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md., USA. friedman@nidcd.nih.gov
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: John T
authors.initials: JT
authors.lastname: Hinnant
authors.forename: Manju
authors.initials: M
authors.lastname: Ghosh
authors.forename: Erich T
authors.initials: ET
authors.lastname: Boger
authors.forename: S
authors.initials: S
authors.lastname: Riazuddin
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Lorraine
authors.initials: L
authors.lastname: Potocki
authors.forename: Edward R
authors.initials: ER
authors.lastname: Wilcox
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000483:Alleles; D001309:Auditory Threshold; D000072259:Connexin 26; D017630:Connexins; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000151:congenital* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009218:Myosins / Q000235:genetics*; D010641:Phenotype
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; C485245:MYO15A protein, human; D000072259:Connexin 26; D009218:Myosins