Journal article
Mutations in the γ-Actin Gene ( ACTG1) Are Associated with Dominant Progressive Deafness (DFNA20/26)
American journal of human genetics, Vol.73(5), pp.1082-1091
2003
DOI: 10.1086/379286
PMCID: PMC1180488
PMID: 13680526
Abstract
Age-related hearing loss (presbycusis) is a significant problem in the population. The genetic contribution to age-related hearing loss is estimated to be 40%–50%. Gene mutations that cause nonsyndromic progressive hearing loss with early onset may provide insight into the etiology of presbycusis. We have identified four families segregating an autosomal dominant, progressive, sensorineural hearing loss phenotype that has been linked to chromosome 17q25.3. The critical interval containing the causative gene was narrowed to ∼2 million bp between markers D17S914 and D17S668. Cochlear-expressed genes were sequenced in affected family members. Sequence analysis of the γ-actin gene (
ACTG1) revealed missense mutations in highly conserved actin domains in all four families. These mutations change amino acids that are conserved in all actins, from protozoa to mammals, and were not found in >100 chromosomes from normal hearing individuals. Much of the specialized ultrastructural organization of the cells in the cochlea is based on the actin cytoskeleton. Many of the mutations known to cause either syndromic or nonsyndromic deafness occur in genes that interact with actin (e.g., the myosins, espin, and harmonin). The mutations we have identified are in various binding domains of actin and are predicted to mildly interfere with bundling, gelation, polymerization, or myosin movement and may cause hearing loss by hindering the repair or stability of cochlear cell structures damaged by noise or aging. This is the first description of a mutation in cytoskeletal, or nonmuscle, actin.
Details
- Title: Subtitle
- Mutations in the γ-Actin Gene ( ACTG1) Are Associated with Dominant Progressive Deafness (DFNA20/26)
- Creators
- M Zhu - Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MIT Yang - Interdepartmental Genetics Program and Department of Otolaryngology, University of Iowa, Iowa CityS Wei - Departments of Genetics Program, Michigan State University, East Lansing, MIA.T DeWan - Laboratory of Statistical Genetics, The Rockefeller University, New YorkR.J Morell - Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MDJ.L Elfenbein - Departments of Audiology & Speech Sciences, Michigan State University, East Lansing, MIR.A Fisher - Departments of Pediatrics & Human Development, Michigan State University, East Lansing, MIS.M Leal - Laboratory of Statistical Genetics, The Rockefeller University, New YorkR. J.H Smith - Interdepartmental Genetics Program and Department of Otolaryngology, University of Iowa, Iowa CityK.H Friderici - Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.73(5), pp.1082-1091
- DOI
- 10.1086/379286
- PMID
- 13680526
- PMCID
- PMC1180488
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2003
- 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
- 9984006418502771
Metrics
32 Record Views