Background: Earlier studies have mapped the autosomal recessive nonsyndromi
c deafness locus, DFNB15, to chromosomes 3q21.3-q25.2 and 19p13.3-13.1, ide
ntifying one of these chromosomal regions (or possibly both) as the site of
a deafness-causing gene. Mutations in unconventional myosins cause deafnes
s in mice and humans. One unconventional myosin, myosin 1F (MYO1F), is expr
essed in the cochlea and maps to chromosome 19p13.3-13.2.
Objective: To evaluate MYO1F as a candidate gene for deafness at the DFNB15
locus by determining its genomic structure and screening each exon for dea
fness-causing mutations to identify possible allele variants of MYO1F segre
gating in the DFNB15 family.
Methods: We used radiation hybrid mapping to localize MYO1F on chromosome a
rm 19p. We next determined its genomic structure using multiple long-range
polymerase chain reaction experiments. Using these data, we completed mutat
ion screening using single-stranded conformational polymorphism analysis an
d direct sequencing of affected and nonaffected persons in the original DFN
Results: Radiation hybrid mapping placed MYO1F in the DFNB15 interval, esta
blishing it as a positional candidate gene. Its genomic structure consists
of 24 coding exons. No mutations or genomic rearrangements were found in th
e original DFNB15 family, making it unlikely that MYO1F is the disease-caus
ing gene in this kindred.
Conclusions: Although we did not find MYO1F allele variants in one family w
ith autosomal recessive nonsyndromic hearing loss, the gene remains an exce
llent candidate for hereditary hearing impairment. Given its wide tissue ex
pression, MYO1F might cause syndromic deafness.