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Mutations in the first MyTH4 domain of MYO15A are a common cause of DFNB3 hearing loss
Journal article   Peer reviewed

Mutations in the first MyTH4 domain of MYO15A are a common cause of DFNB3 hearing loss

A Eliot Shearer, Michael S Hildebrand, Jennifer A Webster, Kimia Kahrizi, Nicole C Meyer, Khadijeh Jalalvand, Sanaz Arzhanginy, William J Kimberling, Dietrich Stephan, Melanie Bahlo, …
The Laryngoscope, Vol.119(4), pp.727-733
04/2009
DOI: 10.1002/lary.20116
PMCID: PMC2885251
PMID: 19274735

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Abstract

To use clinical and genetic analyses to determine the mutation causing autosomal recessive nonsyndromic hearing loss (ARNSHL) segregating in two consanguineous Iranian families. Family study. Members of each family received otologic and audiometric examination for the type and extent of hearing loss. Linkage mapping using Affymetrix 50K GeneChips and short tandem repeat (STRP) analysis localized the hearing loss in both families to the DFNB3 locus. Direct sequencing of the MYO15A gene was completed on affected members of both families. Family L-3165 segregated a novel homozygous missense mutation (c.6371G>A) that results in a p.R2124Q amino acid substitution in the myosin XVa protein, while family L-896 segregated a novel homozygous missense (c.6555C>T) mutation resulting in a p.P2073S amino acid change. These are the first MYO15A mutations reported to cause DFNB3 sensorineural hearing loss in the Iranian population. Like other mutations located in the myosin tail homology 4 (MyTH4) domain, the p.R2124Q and p.P2073S mutations are predicted to disrupt the function of the myosin XVa protein, which is integral to the mechanosensory activity of hair cells in the inner ear.
Humans Genotype Male Chromosome Mapping Hearing Loss, Sensorineural - genetics Mutation, Missense Myosins - genetics Chromosomes, Human, Pair 17 - genetics Lod Score Sequence Analysis, Protein Iran Pedigree Female Consanguinity

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