Mutation Screening And Whole Spectrum Mutation Map Drawing Of GJB2 Gene Among Non-syndromic Hearing Impairment Patients

For the past 10 years, there has made remarkable progress about hereditary hearing loss. Since the first deafness gene was cloned in 1995, 128 loci and more than 40 karyogenes for NSHI (non-syndromic hearing impairment) have been identified. These genes encode a wide variety of proteins: from cytoskeletal proteins, extracellular matrix proteins, channels and gap junction components, to transcription factors and unknown proteins. GJB2 gene mutation accounts for 50% autosomal recessive NSHI. The screening of GJB2 gene mutation will assist us with genetic counseling, and it should be a rout detection to screen GJB2 gene mutation for severe or profound hearing loss. We used the plenty genetic resources established by the Otolaryngology Institute , Genetic Testing Center for Deafness of PLA General Hospital, to collect information of NSHI patients, and to investigate the molecular epidemiology of GJB2 gene in Chinese NSHI cases.Part one: collection of clinical data and mutation screening of theGJB2 235delC in NSHI casesGJB2 gene mutations were the major cause for autosomal recessive NSHI. More than 40 genes for NSHI have been identified. About 50% autosomal recessive NSHI was caused by GJB2 gene mutations. This study addressed the molecular epidemiology of GJB2 gene, identified the mutational hot spot and genetic features of GJB2 gene in Chinese population. This founding provide basic information to genetic diagnosis in Chinese population.Part two: mapping ofGJB2 gene mutations of Chinese NSHI casesSince GJB2 gene was cloned in 1997, over 80 mutant had been identified: from shearing mutation, nonsense mutation, missense mutation to frameshift mutation and other mutations. We detected complete sequence of GJB2 gene for mutations in 1190 NSHI cases, and found changed sequence in 69.33% ones, identified the mutational hot spot. 40 sequence changing was found, and seven new mutations were identified in this study. Genotype-phenotype correlation for the 235delC mutations was evaluated. In short, this study characterized the profile of the map of GJB2 genetic variations in Chinese NSHI cases. These data provide basic information to foster genetic approaches to the early diagnosis and prediction of recurrent risks for hearing impairment in Chinese population.