CAJ | 학술논문

目的分析探讨一个连续七代表现为常染色体显性遗传性非综合征型迟发性耳聋家系的临床表型及遗传学特征.方法 2011年8月对浙江省-耳聋家系成员进行病史采集、全身及听力学检查,绘制遗传图谱并进行遗传学特征分析.通过常规PCR扩增及Sanger测序方法筛查GJB2、MTRNRl (12SrRNA)、SLC26A4基因致病突变.使用定向捕获联合二代测序技术,对包括所有已知非综合征型耳聋的79个耳聋相关基因的外显子及其侧翼内含子序列进行筛查.结果该耳聋家系共七代,现存家系成员73人,符合常染色体显性遗传规律,参与本研究的22人中耳聋患者11人,除1人为语前聋外,其他患者均表现为迟发性、渐进性听力下降,发病年龄9～30岁,听力曲线多为平坦型.对常见耳聋基因GJB2、MTRNRl (12SrRNA)、SLC26A4进行筛查,排除了致病突变.使用定向捕获联合二代测序技术,先证者(Ⅴ:6)在发现的70个插入缺失标记(insertion-deletion,InDel)和591个单核苷酸基因多态性(single nucleotide polymorphism,SNP)中,经数据分析滤过后确定3个潜在致病突变位点:COL4A3(c.C1295T)、KCNQl(c.T1058C)和MYH14(c.G1295A).但后续经测序验证,此3个可疑突变位点在家系中不与耳聋表型共分离,从而排除了致病可能.结论该常染色体显性非综合征型迟发性耳聋大家系基本排除了79个耳聋相关基因的点突变及小片段插入缺失突变的可能,其为新基因致病的可能性较大.
목적 분석탐토일개련속칠대표현위상염색체현성유전성비종합정형지발성이롱가계적림상표형급유전학특정.방법 2011년8월대절강성-이롱가계성원진행병사채집、전신급은역학검사,회제유전도보병진행유전학특정분석.통과상규PCR확증급Sanger측서방법사사GJB2、MTRNRl (12SrRNA)、SLC26A4기인치병돌변.사용정향포획연합이대측서기술,대포괄소유이지비종합정형이롱적79개이롱상관기인적외현자급기측익내함자서렬진행사사.결과 해이롱가계공칠대,현존가계성원73인,부합상염색체현성유전규률,삼여본연구적22인중이롱환자11인,제1인위어전롱외,기타환자균표현위지발성、점진성은력하강,발병년령9～30세,은력곡선다위평탄형.대상견이롱기인GJB2、MTRNRl (12SrRNA)、SLC26A4진행사사,배제료치병돌변.사용정향포획연합이대측서기술,선증자(Ⅴ:6)재발현적70개삽입결실표기(insertion-deletion,InDel)화591개단핵감산기인다태성(single nucleotide polymorphism,SNP)중,경수거분석려과후학정3개잠재치병돌변위점:COL4A3(c.C1295T)、KCNQl(c.T1058C)화MYH14(c.G1295A).단후속경측서험증,차3개가의돌변위점재가계중불여이롱표형공분리,종이배제료치병가능.결론 해상염색체현성비종합정형지발성이롱대가계기본배제료79개이롱상관기인적점돌변급소편단삽입결실돌변적가능,기위신기인치병적가능성교대.
Objective To investigate the clinical and genetic characteristics of a large family with late-onset,progressive autosomal dominant non-syndromic hearing loss.Methods Collections of detail history hereditary features,physical and audiological examination were performed.After mutation screening of GJB2,SLC26A4,MTRNR1 (12SrRNA) genes by Sanger sequencing,the proband was investigated by targeted next-generation sequencing of 79 deafness genes.Results This family included seven generations and 73 members.Eleven persons with hearing loss and 11 normal-hearing persons participated in this study.All affected members but one exhibited late-onset,progressive non-syndromic sensorineural hearing loss; the ages of onset were between 9 and 30 years.Mutation screening by sanger-sequencing and targeted next-generation sequencing excluded the possibility of pathogenic mutations within known deafness gene.Conclusions A Chinese family with late-onset progressive non-syndromic sensorineural hearing loss was investigated clinically and genetically.By candidate gene approach and targeted next-generation sequencing,this family was preliminary proved to be caused by unknown deafness gene.