Preliminary Mapping Of A Non-syndromic Autosomal Dominant Hereditary Deafness Gene By A Next Generation Sequencing Technique

Objective: to analyze the audiology and genetic characteristics of a deaf family,and to preliminarily locate the pathogenic gene by using the new generation sequencing technology.To provide genetic counselling for the family and to guide eugenics.Methods: by means of detailed history,some members of a family deafness carefully audiological testing and systemic physical examination,the quantitative collection of peripheral blood samples,family mapping,by analyzing characteristics of the family members of the phenotype and the family of genetic approach;Extraction of peripheral blood DNA with high throughput sequencing of three core family members to capture of target area 127 deafness genes,through screening library retrieval,one thousand frequency and predicting protein function after the application of candidate genes,in the end,Sanger sequencing candidate genes in the rest of the family members of the boc verification,the analysis of the phenotype and genotype were separated.Results: a 4-generation continuous genetic hereditary deafness family was co llected,with 41 people in the family and 39 existing ones,including 17 males and 22 females.Combined with the history,6 men and 7 women were diagnosed with the history of deafness.Among them,the oldest person was 56 years old,and the youngest was born with disease,and 11 samples of peripheral blood were collected.Besides II6 pure tone audiometry is high frequency decline moderately sensorineural deafness ears symmetry,the remaining members of specific diagnosis deafness（II5,III10,III16,III17,IV8,IV12）are characterized by ears symmetry all frequency heavy-extremely severe sensorineural deafness.Besides II6 performance language for the deaf,the rest of the 6 patients with diagnosis of deafness hearing are characterized by bilateral symmetry heavy-extremely severe sensorineural deafness,childhood onset,their hearing before learning to speak,the hearing loss has no obvio us progress.The family members are deaf patients for four generations,each generation of members of the men and women are sick,and the ratio is close to the men and women,deafness phenotype from generation to generation,so determine the genealogy of autosomal dominant hereditary deafness family.The target sequence of 127 deafness genes was screened by three core family members（the first witness and their parents）,and three mutation candidate genes were selected（KCNE1）.NM₀00219;C.260 G > A;P.t.rp87 Ter heterozygous mutation,GJB2;NM₀04004;C.109 G > A;P.V a137 l le/p.V37 I heterozygous mutation,WFS1 NM₀06005;C.2606 G > A;P.er869 Asn heterozygous mutations),the remaining eight family members for the three candidate genes of Sanger sequencing method validation,combined with family genetic methods,candidate genes coding protein function prediction and the family members of sequencing,one candidate genes KCNE1 c.260 G > A heterozygous mutations in the line of the deaf shall conform to the phenotype and genotype were separated,speculated that its quite possible for the family disease genes.Conclusion: the collected family as an autosomal dominant syndrome type of hereditary deafness family,found that the deaf family members are characterized by bilateral,congenital,symmetry,heavy-extremely severe sensorineural deafness.Using high-throughput sequencing technology to capture the sequencing technology,successfully locate the pathogenic gene mutation of the deaf people.The heterozygous mutation of KCNE1 c.260G>A gene found in this study is the first reported by KCNE1 gene as non-syndromic autosomal dominant inheritance,so it is of great significance to the expansion of the human deafness genome library.