本文選題：聽神經(jīng)病 + 全外顯子測序��； 參考：《南京醫(yī)科大學學報(自然科學版)》2017年08期

【摘要】：目的 :在多年圍繞1個常染色體顯性遺傳性非綜合征型聽神經(jīng)病家系開展系統(tǒng)分子遺傳學研究的基礎上,進一步探討該家系耳聾的致病機制,以期發(fā)現(xiàn)新的聽神經(jīng)病致病基因和突變位點。方法:對3例耳聾患者和1例配偶進行全外顯子組測序,初步篩選出與家系耳聾相關的候選致病基因。采用PCR-Sanger測序法,檢測上述候選基因變異是否與家系表型共分離。最后,以50例與研究家系無關的聽力正常人為對照,檢測候選致病突變在正常群體中的突變頻率和SNPs遺傳多態(tài)性。結果:全外顯子測序分析得到41個候選致病基因突變;用PCR-Sanger測序法對核心家系的9名成員和2名家系外聽力正常人進行驗證,僅發(fā)現(xiàn)1個基因突變(ALOX15B 7942797 CT)與家系耳聾表型共分離。選取50例家系外正常對照的DNA樣本對ALOX15B基因進行PCR擴增和序列分析,結果顯示有2例聽力正常人也檢測到該基因的同一變異,提示該變異為SNPs遺傳多態(tài)性。結論:對核心家系成員的全外顯子組測序分析和Sanger測序法驗證未發(fā)現(xiàn)有意義的突變位點,排除了該家系耳聾由基因編碼區(qū)突變及Indels致病的可能性。
[Abstract]:Objective: to investigate the pathogenesis of deafness in an autosomal dominant hereditary non-syndromic auditory neuropathy family based on systematic molecular genetic studies for many years. In order to find a new pathogenicity gene and mutation site of auditory neuropathy. Methods: three deafness patients and one spouse were sequenced and the candidate genes associated with deafness were preliminarily screened. PCR-Sanger sequencing was used to detect whether the mutation of the candidate gene was coisolated from the pedigree phenotype. Finally, the mutation frequency and SNPs genetic polymorphism of candidate pathogenetic mutations in normal population were detected in 50 normal subjects unrelated to the study family. Results: 41 candidate gene mutations were obtained by total exon sequencing, 9 members of nuclear family and 2 individuals with normal hearing outside of nuclear family were tested by PCR-Sanger sequencing. Only one gene mutation (ALOX15B 7942797 CT) was coisolated from the deafness phenotype. The ALOX15B gene was amplified by PCR and sequenced from 50 normal controls. The results showed that the same mutation of ALOX15B gene was detected in 2 normal people, indicating that the mutation was SNPs genetic polymorphism. Conclusion: no significant mutation sites were found in the whole exon sequence analysis and Sanger sequencing of nuclear family members, which excluded the possibility of gene coding mutation and Indels pathogenicity of deafness in this family.
【作者單位】： 南京醫(yī)科大學第一附屬醫(yī)院耳鼻咽喉科;南京醫(yī)科大學生物技術系;
【分類號】：R764

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本文編號：2063936