The Screening And Mutation Analysis Of A Family With Non-syndromic Hearing Loss

Part 1:Clinical characters and screening for common deafness genes of a family with non-syndromic hearing lossObjective:A family with non-syndromic hearing loss was employed for genetic analyses of common deafness genes, inclusive of GJB2, GJB3, SLC26A4, mitochondria 12S rRNA, in which nine mutations were screened.Methods:We did comprehensive survey on the family members with sensorineural hearing loss and drew a genetic pedigree chart. General health status was investigated and medical history was inquired about whether they had trauma or otitis media. Comprehensive physical examination was conducted. The audiological and vestibular functions were examined. The imagings of the inner ear and skull were studied. The peripheral blood was extracted from the family members. DNA was extracted from peripheral blood using the DNA kit and was amplified by PCR, using GeeDom nine hereditary deafness gene detection kit (microarray method) to do common genetic screening for one of the deaf family members.Results:Besides deafness of these family members, no other system abnormality and deformed cochlea was found. Auditory nerve pathway and brainstem were found to be normal. The pedigree was characterized by non-syndromic deafness with full-frequency hearing loss in an autosomal dominant heredity model. The results showed that the nine mutations of common deafness genes (GJB2, GJB3, SLC26A4, mitochondria 12S rRNA) had no variation.Conclusion:Pedigree analyses show it is inherited in an autosomal-dominant pattern. Hearing loss is characterized by congenital, progressive, and bilateral symmetrical deafness. Degree of deafness is different between individuals at the same ages. The preliminary molecular genetic analyses suggest known deafness locus seems not contribute to the pathogenesis of the hearing loss in this Chinese family, which indicates new genes or mutations involved.Part 2:Mutation analysis of a family with non-syndromic hearing loss by exome sequencingObjective:Hearing loss is the most common sensory disorder, and more than 60% of people suffering from hearing loss can be attributed to genetic causes. Although many mutant loci have been linked to hereditary hearing impairment, most of the causative loci have not yet been identified. The goal of this study is to identify the mutant locus of an autosomal-dominant inherited sensorineural hearing loss in all-frequency in a Chinese six-generation family.Methods:We performed exome sequencing of one family member with normal hearing and three patients to screen responsible candidate genes from the known genes in the gene database and the genes of the family members. Sequencing and symptom were also compared between this family and people outside the family to confirm the variant mutations.Results:A novel missense mutation c.2389G>A (GACâ†'AAC) in WFS1 gene was identified, which was co-segregated with the phenotype in this family. No mutation in this locus was found in 200 persons with normal hearing.Conclusion:A novel mutation in WFS1 gene (c.2389G>A) may cause autosomal-dominantly sensorineural inherited hearing loss in all frequencies.