Genome-Wide Scanning For A Nonsyndromic Autosomal Dominant Deafness In A Six-Generation Family

A disease-causing gene responsible for hereditary hearing impairment in a six-generation family was localized to chromosome 9. It is first time that we Chinese defined a nonsyndromic autosomal dominant deafness gene locus (DFNA) by ourselves. Based on the regulation of Human Gene Nomenclature, the novel DFNA is designated as DFNA 23.Family investigation demonstrated that hearing impairment in the family is inherited in a classic autosomal dominant mode and passed along is six generations. Diagnosis of nonsyndromic autosomal dominant , progressive neurosensory hearing loss was based on the medical history , physical examination and audiological evaluation of the family numbers. It is inferred that the hearing loss begins in the first decade of life or early second decade of life, according to the medical history and audiometry, and it first affected high frequence mildly, then progressed in turn to mid and low frequencies quickly. finally, all affected member in the family became severe to profound deafness at age of 30 or above. The pure tune audiometry of both air and bone conduct showed neurosensory deafness, and cochlear sensory hearing loss is confirmed in hereditary deafness of 43 ears from 28 cases.Allele sharing analysis was carried out with previously reported genetic markers linked to known DFNA loci. As result of it, no evidence of linkage of the gene responsible for merged. On the basis of the allele sharing study, a genome-wide scaning was performend with ABI PRISM^TM Linkage Mapping Set Version 2.0 for the DFNA in the family. Two-point linkage analysis has been done by use of Mlink program of Linkage package 5.2. We found that the hereditary deafness in the family is allele heterogenous, because no evidence of linkage of disease-causing gene for the DFNA in the family was confirmed with 285 polymorphism markers available, when a single big pedigree file was used. However, when two pedigree files were combined for linkage analysis, which was made up respectively from branch A and B, we obtained significant Lod score above 3, for marker N12, when theta=0, Zmax=3.77, Nf1, theta=0.05, Zmax=3.22; and D4S403, when theta=0, Zmax=2.22, which showed suggestive evidence of linkage. The results demostrated comfirmative evidence of linkage of a gene responsible for the DFNA in the family with a location on chromosome harbourng Marker N11. As for D4S403, whereas there is a big gap of 20 cM or...