本文選題：聽(tīng)神經(jīng)病 + 全外顯子測(cè)序��； 參考：《南京醫(yī)科大學(xué)學(xué)報(bào)(自然科學(xué)版)》2017年08期

【摘要】：目的 :在多年圍繞1個(gè)常染色體顯性遺傳性非綜合征型聽(tīng)神經(jīng)病家系開(kāi)展系統(tǒng)分子遺傳學(xué)研究的基礎(chǔ)上,進(jìn)一步探討該家系耳聾的致病機(jī)制,以期發(fā)現(xiàn)新的聽(tīng)神經(jīng)病致病基因和突變位點(diǎn)。方法:對(duì)3例耳聾患者和1例配偶進(jìn)行全外顯子組測(cè)序,初步篩選出與家系耳聾相關(guān)的候選致病基因。采用PCR-Sanger測(cè)序法,檢測(cè)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(wú)關(guān)的聽(tīng)力正常人為對(duì)照,檢測(cè)候選致病突變?cè)谡Ｈ后w中的突變頻率和SNPs遺傳多態(tài)性。結(jié)果:全外顯子測(cè)序分析得到41個(gè)候選致病基因突變;用PCR-Sanger測(cè)序法對(duì)核心家系的9名成員和2名家系外聽(tīng)力正常人進(jìn)行驗(yàn)證,僅發(fā)現(xiàn)1個(gè)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(duì)照的DNA樣本對(duì)ALOX15B基因進(jìn)行PCR擴(kuò)增和序列分析,結(jié)果顯示有2例聽(tīng)力正常人也檢測(cè)到該基因的同一變異,提示該變異為SNPs遺傳多態(tài)性。結(jié)論:對(duì)核心家系成員的全外顯子組測(cè)序分析和Sanger測(cè)序法驗(yàn)證未發(fā)現(xiàn)有意義的突變位點(diǎn),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(xué)第一附屬醫(yī)院耳鼻咽喉科;南京醫(yī)科大學(xué)生物技術(shù)系;
【分類(lèi)號(hào)】：R764

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本文編號(hào)：2063935