关键词: 连锁分析, 基因定位, DFNA9, 耳聋

Abstract:

Hereditary non-syndromic sensorineural hearing loss is a genetically highly heterogeneous group of disorders. To date, at least 50 loci for autosomal dominant non-syndromic sensorineural hearing loss (DFNA) have been identified by linkage analysis. Here we report a huge family with late onset autosomal dominant hereditary non-syndromic hearing loss. In this family, 73 of 170 family members have been conducted physical examination, pure-tone audiometry, immittance testing and auditory brainstem response testing (ABR). The results indicated that 39 of 73 tested family members have sensorineural hearing loss in various degrees. No associated visible abnormalities in other systems were found in this family. After exclusion of the 14 known DFNA loci with markers from the Hereditary Hearing Loss Homepage (URL: http://dnalab-www.uia.ac.be/dnalab/hhh), a genome wide scan was carried out using 382 highly informative microsatellite markers at approximately 9.2 cM intervals throughout the genome. Linkage analysis was carried out under a fully penetrant autosomal dominant mode of inheritance with no phenocopies. A maximum two-point LOD score of 6.69 at theta=0 was obtained for marker D14S1040. Haplotype analysis placed the locus within a 7.6 cM genetic interval defined by marker D14S1021 and D14S70, overlapping with the DFNA9 locus.