Is DFNA5 a susceptibility gene for age-related hearing impairment?
A mutation in DFNA5 leads to a type of hearing loss that closely resembles the frequently observed age-related hearing impairment (ARHI). The hearing loss is sensorineural, progressive and starts at the high frequencies. As DFNA5 was considered an excellent candidate ARHI susceptibility gene, we performed linkage analysis to a quantitive measure of high frequency hearing loss. However, no significant linkage between ARHI and microsatellite markers from the DFNA5 region could be detected. Subsequently, the DFNA5 coding region was analysed for single nucleotide polymorphisms (SNPs). Two SNPs leading to amino-acid substitutions (P142H and V207M) were selected for further analysis. Using these SNPs, an association study based on a collection of random individuals, and a case-control association study were performed. No significant differences in genotypes between good hearing and hearing impaired individuals could be detected in either study design. We conclude that there exists no strong association between DFNA5 and ARHI.
Van Laer
Lut
L
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
DeStefano
Anita L
AL
Myers
Richard H
RH
Flothmann
Kris
K
Thys
Sofie
S
Fransen
Erik
E
Gates
George A
GA
Van Camp
Guy
G
Baldwin
Clinton T
CT
D000375:Aging / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci; D011960:Receptors, Estrogen; D000094524:Gasdermins
D002352:Carrier Proteins; D011960:Receptors, Estrogen; C111432:GSDME protein, human; D000094524:Gasdermins