 |
|
MYO1F as a Candidate Gene for Nonsyndromic Deafness, DFNB15
Achih H. Chen, MD;
Dietrich A. Stephan, PhD;
Tama Hasson, MD;
Kunihiro Fukushima, MD;
Christiana M. Nelissen, BA;
Arthur F. Chen, BS;
Andrew I. Jun, MD;
Arabandi Ramesh, PhD;
Guy Van Camp, PhD;
Richard J. H. Smith, MD
Arch Otolaryngol Head Neck Surg. 2001;127:921-925.
Background Earlier studies have mapped the autosomal recessive nonsyndromic deafness
locus, DFNB15, to chromosomes 3q21.3-q25.2 and 19p13.3-13.1,
identifying one of these chromosomal regions (or possibly both) as the site
of a deafness-causing gene. Mutations in unconventional myosins cause deafness
in mice and humans. One unconventional myosin, myosin 1F (MYO1F), is expressed 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 deafness-causing mutations to identify possible
allele variants of MYO1F segregating in the DFNB15 family.
Methods We used radiation hybrid mapping to localize MYO1F on chromosome arm 19p. We next determined its genomic structure using
multiple long-range polymerase chain reaction experiments. Using these data,
we completed mutation screening using single-stranded conformational polymorphism
analysis and direct sequencing of affected and nonaffected persons in the
original DFNB15 family.
Results Radiation hybrid mapping placed MYO1F in the DFNB15 interval, establishing it as a positional candidate
gene. Its genomic structure consists of 24 coding exons. No mutations or genomic
rearrangements were found in the original DFNB15
family, making it unlikely that MYO1F is the disease-causing
gene in this kindred.
Conclusions Although we did not find MYO1F allele variants
in one family with autosomal recessive nonsyndromic hearing loss, the gene
remains an excellent candidate for hereditary hearing impairment. Given its
wide tissue expression, MYO1F might cause syndromic
deafness.
From the Departments of Otolaryngology and Pediatrics, University of
Iowa, Iowa City (Drs A. H. Chen, Jun, and Smith, Ms Nelissen, and Mr A. F.
Chen); the Cancer Genetics Branch, National Human Genome Research Institute/National
Institutes of Health, Bethesda, Md (Dr Stephan); the Department of Biology,
Yale University, New Haven, Conn (Dr Hasson); the Department of Otolaryngology,
Okayama University Medical School, Okayama, Japan (Dr Fukushima); the Department
of Genetics, University of Madras, Madras, India (Dr Ramesh); and the Department
of Medical Genetics, University of Antwerp, Antwerp, Belgium (Dr Van Camp).
RELATED ARTICLE
Archives of Otolaryngology–Head & Neck Surgery Reader's Choice: Continuing Medical Education
Arch Otolaryngol Head Neck Surg. 2001;127(8):1011-1012.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Modulation of cell adhesion and motility in the immune system by Myo1f.
Kim et al.
Science 2006;314:136-139.
ABSTRACT
| FULL TEXT
|
