A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family.
Hearing loss is the most common sensory disorder in humans, and genetic factors are a major cause. Approximately 15-20% of genetic cases exhibit an autosomal dominant pattern of transmission. So far, 41 autosomal dominant loci have been mapped and 17 genes have been identified. Here we report the mapping of a novel locus for autosomal dominant non-syndromic hearing loss, DFNA47, to chromosome 9p21-22 in a large multigenerational Italian family with progressive hearing impairment. Most affected individuals noticed hearing impairment after their teens with subsequent gradual progression to a moderate-severe loss. There were no obvious vestibular dysfunction and other associated abnormalities. A maximum lod score of 3.14 was obtained with marker D9S157 (at theta=0) after a genome wide search. The study of additional markers allowed us to confirm this region with positive lod scores of 3.58 (at theta=0 from D9S285) and of 3.67 (at theta=0 from D9S162). Recombinants define a region of approximately 9 cM flanked by markers D9S268 and D9S942. Multipoint linkage analysis showed a Lod score of 4.26. Few known genes map to the region, and those possibly related by function to hearing are being screened for disease-causing mutations.
D'Adamo
Pio
P
TIGEM (Telethon Institute of Genetics and Medicine), 80131 Naples, Italy.
Donaudy
Francesca
F
D'Eustacchio
Angela
A
Di Iorio
Enzo
E
Melchionda
Salvatore
S
Gasparini
Paolo
P
D000293:Adolescent; D000328:Adult; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D005260:Female; D005799:Genes, Dominant; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree