Genetic analysis of presbycusis by arrayed primer extension.
Using the Hereditary Hearing Loss arrayed primer extension (APEX) array, which contains 198 mutations across 8 hearing loss-associated genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, 12S-rRNA, and tRNA Ser), we compared the frequency of sequence variants in 94 individuals with early presbycusis to 50 unaffected controls and aimed to identify possible genetic contributors. This cross-sectional study was performed at Stanford University with presbycusis samples from the California Ear Institute. The patients were between ages 20 and 65 yr, with adult-onset sensorineural hearing loss of unknown etiology, and carried a clinical diagnosis of early presbycusis. Exclusion criteria comprised known causes of hearing loss such as significant noise exposure, trauma, ototoxic medication, neoplasm, and congenital infection or syndrome, as well as congenital or pediatric onset. Sequence changes were identified in 11.7% and 10% of presbycusis and control alleles, respectively. Among the presbycusis group, these solely occurred within the GJB2 and SLC26A4 genes. Homozygous and compound heterozygous pathogenic mutations were exclusively seen in affected individuals. We were unable to detect a statistically significant difference between our control and affected populations regarding the frequency of sequence variants detected with the APEX array. Individuals who carry two mild mutations in the GJB2 gene possibly have an increased risk of developing early presbycusis.
Rodriguez-Paris
Juan
J
Department of Pathology, L235, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Ballay
Charles
C
Inserra
Michelle
M
Stidham
Katrina
K
Colen
Tahl
T
Roberson
Joseph
J
Gardner
Phyllis
P
Schrijver
Iris
I
D000328:Adult; D000368:Aged; D027321:Anion Transport Proteins / Q000235:genetics; D000072259:Connexin 26; D000075302:Connexin 30; D018031:Connexin 43 / Q000235:genetics; D017630:Connexins / Q000235:genetics; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011304:Presbycusis / Q000175:diagnosis / Q000235:genetics*; D000076988:Sulfate Transporters
D027321:Anion Transport Proteins; D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; D017931:DNA Primers; C500216:GJA1 protein, human; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; C498719:SLC26A5 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26; C068044:GJB3 protein, human