| Hearing loss is a common sensory disorder in the human population. The incidence of congenital hearing loss is estimated at 1 in 1,000 births, of which approximately equal numbers of cases are attributed to environmental and genetic factors. Of the hearing-loss disorders attributable to genetic causes, ~70% are classified as nonsyndromic and the remaining 30% as syndromic. Among the many disorders classified as syndromic hearing loss, the pathology varies widely, but, in nonsyndromic deafness, the defect is generally sensorineural. Nonsyndromic hearing impairment can be further subdivided by mode of inheritance: ~70% of cases are autosomal recessive, 22% are autosomal dominant, 1% are X-linked, and <1% are due to mitochondrial inheritance. Dominant loci are denoted with the prefix "DFNA", recessive loci with "DFNB", X-linked loci with "DFN", and modifying loci with "DFNM". Generally, patients with autosomal recessive hearing impairment have prelingual and profound deafness, and patients with autosomal dominant hearing impairment have progresswive and postlingual hearing impairment. This observation may be explained by the complete absence of functional protein in patients with recessive disorders, whereas, in patients with autosomal dominant disorders, dominant mutations may be consistent with initial function and subsequent hearing impairment due to accumulation of pathology.Over the past 5 years, remarkable progress has been made in theidentification of new loci for nonsyndromic hearing impairment (NSHL) and in the cloning of deafness genes. To date, 77 loci have been reported for nonsyndromic deafness: 40 autosomal dominant, 30 autosomal recessive, and 7 X-linked. In addition, 51 auditory genes have been identified: 15 for autosomal dominant NSHI loci, 9 for autosomal recessive NSHL loci, 2 for X-linked NSHL loci, 5 mitochondrial, and ^ 32 genes for syndromic hearing loss (some genes cause multiple forms of deafness). Although significant advances have been made, there is no doubt that many more genes await discovery. Identifying these genes and characterizing the proteins they encode will increase our knowledge of the molecular processes involved in the auditory system and will improve our understanding of how such processes can become altered and lead to hearing impairment.In our research, we first successfully established a network for collecting genetic resources of hearing impairment in China. During the research, we had collected 20 pedigrees with various deafness phenotypes. In our study, we were lucky for finding a Y-linked inheritance pattern with nonsyndromic progressive hearing loss in a large seven generations Chinese family. The maximum reliability for the existence of Y-linked inheritance pattern in the hereditary hearing impairment was elucidated by genetic approach through pedigree analysis, excluding candidate gene on X-chromosome and excluding linkage of autosomal chromosome markers to our family. In our study, we also mapped a locus on 19q13.2-q13.32 in a Chinese nonsyndromic autosomal dominant progressive hearing loss family. These studies were composed of three parts below:PART 1: Collecting, characterizing of the genetic resource for hereditary hearing impairmentThe purpose of the study was to establish a repository consisting of DNA samples, immortalized cell lines (from which DMA can be extracted continuously), and accompanying clinical and pedigree data. In our study, we first successfully established a network for collecting genetic resources of hearing loss in China. We obtained the information of the deafness resources through the network and collected the resources including DNA samples, immortalized cell lines, and accompanying clinical and pedigree data according to international standards. We had collected 20 pedigrees including syndromic and nonsyndromic hereditary hearing loss. All that included one large family of hearing loss with Y-linked inheritance pattern, one family of X-linked recessive nonsyndromic hereditary hearing impairment, ten p...
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