G2Cdb::Human Disease report

Disease id
D00000221
Name
Hearing loss (age-related)
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00002443 SERPINA3
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3
Y (13680526) Microinsertion (MI) Y

References

  • Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26).

    Zhu M, Yang T, Wei S, DeWan AT, Morell RJ, Elfenbein JL, Fisher RA, Leal SM, Smith RJ and Friderici KH

    Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.

    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 approximately 2 million bp between markers D17S914 and D17S668. Cochlear-expressed genes were sequenced in affected family members. Sequence analysis of the gamma-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.

    Funded by: Intramural NIH HHS: Z01 DC000039; NIDCD NIH HHS: 1Z01DC00039-06, DC03594, R01 DC003544, R01 DC003594, R01 DC004568, R01-DC03544, R01-DC04568, R29 DC003594

    American journal of human genetics 2003;73;5;1082-91

Literature (1)

Pubmed - human_disease

  • Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20/26).

    Zhu M, Yang T, Wei S, DeWan AT, Morell RJ, Elfenbein JL, Fisher RA, Leal SM, Smith RJ and Friderici KH

    Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.

    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 approximately 2 million bp between markers D17S914 and D17S668. Cochlear-expressed genes were sequenced in affected family members. Sequence analysis of the gamma-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.

    Funded by: Intramural NIH HHS: Z01 DC000039; NIDCD NIH HHS: 1Z01DC00039-06, DC03594, R01 DC003544, R01 DC003594, R01 DC004568, R01-DC03544, R01-DC04568, R29 DC003594

    American journal of human genetics 2003;73;5;1082-91

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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