Objectives: To use clinical and genetic analyses to determine the mutation causing autosomal recessive nonsyndromic hearing loss (ARNSHL) segregating in two consanguineous Iranian families.
Study design: Family study.
Methods: 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.
Results: 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.
Conclusions: 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.