Journal article
Mutations in LOXHD1, an Evolutionarily Conserved Stereociliary Protein, Disrupt Hair Cell Function in Mice and Cause Progressive Hearing Loss in Humans
American journal of human genetics, Vol.85(3), pp.328-337
2009
DOI: 10.1016/j.ajhg.2009.07.017
PMCID: PMC2771534
PMID: 19732867
Abstract
Hearing loss is the most common form of sensory impairment in humans and is frequently progressive in nature. Here we link a previously uncharacterized gene to hearing impairment in mice and humans. We show that hearing loss in the ethylnitrosourea (ENU)-induced
samba mouse line is caused by a mutation in
Loxhd1. LOXHD1 consists entirely of PLAT (polycystin/lipoxygenase/α-toxin) domains and is expressed along the membrane of mature hair cell stereocilia. Stereociliary development is unaffected in
samba mice, but hair cell function is perturbed and hair cells eventually degenerate. Based on the studies in mice, we screened DNA from human families segregating deafness and identified a mutation in
LOXHD1, which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL).
LOXHD1,
MYO3a, and
PJVK are the only human genes to date linked to progressive ARNSHL. These three genes are required for hair cell function, suggesting that age-dependent hair cell failure is a common mechanism for progressive ARNSHL.
Details
- Title: Subtitle
- Mutations in LOXHD1, an Evolutionarily Conserved Stereociliary Protein, Disrupt Hair Cell Function in Mice and Cause Progressive Hearing Loss in Humans
- Creators
- Nicolas Grillet - Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USAMartin Schwander - Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USAMichael S Hildebrand - Department of Otolaryngology—Head and Neck Surgery, University of Iowa City, IA 55242, USAAnna Sczaniecka - Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USAAnand Kolatkar - Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USAJanice Velasco - Genome Institute of the Novartis Research Foundation, San Diego, CA 92121, USAJennifer A Webster - Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USAKimia Kahrizi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, IranHossein Najmabadi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, IranWilliam J Kimberling - Department of Genetics, Boys Town National Research Hospital, Omaha, NE 68131, USADietrich Stephan - Genome Institute of the Novartis Research Foundation, San Diego, CA 92121, USAMelanie Bahlo - Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052 VIC, AustraliaTim Wiltshire - Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27516, USALisa M Tarantino - Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27516, USAPeter Kuhn - Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USARichard J.H Smith - Department of Otolaryngology—Head and Neck Surgery, University of Iowa City, IA 55242, USAUlrich Müller - Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.85(3), pp.328-337
- DOI
- 10.1016/j.ajhg.2009.07.017
- PMID
- 19732867
- PMCID
- PMC2771534
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2009
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006410002771
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