The Relationship Genotype For Late-onset Progressive Hearing Loss

Objective: To explore the genetic deafness-related family, and provide some genetic counseling and marriage and childbearing guidance for deaf family. Deafness is the most common disorders that barriers to human communication.The main factors is thought to be hereditary, and mutated genes associated with deafness are not uncommon in the normal group. Tough lots of genes were found associated with hereditary deafness, there are still lots of deaf patients unable to determine their causes.In this study, we have recruited 2 Chinese families with late-onset hearing loss. We analyzed the relationship between phenotype and genotype of the 2 families and hope to capture new mutated genes to enrich the hereditary deafness pathogenic gene pool.Methods: We collect the two family’s information and numbered: HBX, J. Routine ENT examination have to do for family to determine the number of cases and the genetic nature of the preliminary determination. Genomic DNA was extracted from peripheral blood leukocytes using a commercially available DNA extraction kit(Qiagen Inc, Valencia, CA) according to the manufacturer’s instructions. Mutation screening was conducted using polymerase chain reaction(PCR) amplification and the exons were directly sequenced. Common hearing-related genes including gap junction beta 2(GJB2), SLC26A4, mitochondrial DNA 12 S r RNA were examined in the family. If the pathogenic mutations were identified, the resultant sequence data were compared with the evaluation samples for alignment with the National Center for Biotechnology Information reference(NCBI) sequence. If not, according to the phenotype of the affected individuals and the gene mutations about dominant hereditary hearing loss which were discovered previously, screening the may candidate genes, if positive, similar with previous. If still not, the next generation of deafness high-throughput genome sequencing was conducted using DNA samples of the family. Candidate mutation was confirmed by Sanger sequencing.Results:1 In the family of J, we first discovered the KCNQ4 gene mutation in Chinese, and the discovery is a new mutation. The mutated gene is c. 887 G>A in exon 6, which resulting in a Missense mutation(p.G296D).The G296 residue is significantly conserved among the other members of the voltage-gated K(+) channel genes superfamily. The hearing loss in these cases affected high frequencies initially and then developed to the middle and low frequencies.The onset of hearing loss between 0-25 years.None of them showed this mutation.2 The rest of family(HBX) found no clear pathogenic gene. The onset of hearing loss between 0-21 years.The genetic still has limitation, there are a large number of deafness gene are not found. The deafness gene still need more clinical cases to enrich.Conclusions:1 Due to heterogeneity the same gene may harbor many different rare severe mutations in unrelated affected individuals;individually rare mutations collectively play a substantial role in causing complex illnesses; the same mutation may lead to different clinical manifestations(phenotypes) in different individuals; and mutations in different genes in the same or related pathways may lead to the same disorder.2 To date, there are still lots of deafness genes in deaf patients unknown, hereditary deafness gene database still to be perfect.