A novel DFNA5 mutation, IVS8+4 A>G, in the splice donor site of intron 8 causes late-onset non-syndromic hearing loss in a Chinese family.
Clin Genet
; 72(5): 471-7, 2007 Nov.
Article
in En
| MEDLINE
| ID: mdl-17868390
ABSTRACT
We report here the clinical, genetic, and molecular characteristics of a large Chinese family exhibiting non-syndromic, late-onset autosomal dominant sensorineural hearing loss. Clinical evaluation revealed variable phenotypes of hearing loss in terms of severity and age-at-onset of disease in these subjects. Genome-wide linkage analysis mapped the disease gene to the DFNA5 locus with a maximum two-point log odds score of 5.39 at [theta] = 0 for marker D7S2457. DNA sequencing of DFNA5 revealed a novel heterozygous IVS8+4 A>G substitution in the splice donor site of intron 8. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed skipping of exon 8 in the mutant transcript. This mutation faithfully cosegregated with hearing loss in the family. In addition, the mutation was absent in 100 unrelated control DNA samples of Chinese origin. The IVS8+4 A>G mutation is predicted to create a shift in the reading frame and introduce a stop codon at position 372, thereby resulting in a prematurely truncated DFNA5 protein. Up to date, a total of four mutations in DFNA5 have been reported to lead to hearing impairment, all of them result in skipping of exon 8 at the mRNA level. Our findings provide further support for the hypothesis that DFNA5-associated hearing loss is caused by a very specific gain-of-function mutation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Introns
/
Family
/
Receptors, Estrogen
/
RNA Splice Sites
/
Hearing Loss
/
Mutation
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Clin Genet
Year:
2007
Document type:
Article
Affiliation country:
China