中华耳鼻咽喉头颈外科杂志
中華耳鼻嚥喉頭頸外科雜誌
중화이비인후두경외과잡지
CHINESE JOURNAL OF OTORHINOLARYNGOLOGY HEAD AND NECK SURGERY
2013年
12期
978-984
,共7页
伍越%梁玲芝%肖红利%阳娅玲%余啸%郑静%方芳%郑斌娇%唐霄雯
伍越%樑玲芝%肖紅利%暘婭玲%餘嘯%鄭靜%方芳%鄭斌嬌%唐霄雯
오월%량령지%초홍리%양아령%여소%정정%방방%정빈교%당소문
听觉丧失%DNA,线粒体%RNA,转移,天冬氨酸%连接蛋白类%突变
聽覺喪失%DNA,線粒體%RNA,轉移,天鼕氨痠%連接蛋白類%突變
은각상실%DNA,선립체%RNA,전이,천동안산%련접단백류%돌변
Hearing loss%DNA,mitochondrial%RNA,transfer,Asp%Connexins%Mutation
目的 通过对携带线粒体tRNAAsp A7551G突变的母系遗传非综合征型耳聋家系进行临床和分子遗传学特征分析,探讨线粒体tRNAAsp基因突变对非综合征型耳聋的影响.方法 收集1个携带线粒体tRNAAsp A7551G突变的非综合征型耳聋家系,对先证者及其家系成员进行听力学检查、线粒体基因组全序列分析和GJB2基因突变检测等.结果 家系内共6人患病,母系成员占4人.先证者线粒体全基因组分析表明,该线粒体基因组含28个多态位点,属于东亚人群A4单体型.其中除A7551G同质性突变外,无其他有功能意义的多态位点.A7551G突变位于线粒体tRNAAsp反密码子环的反密码子旁高度保守区的第37位,保守性指数为100％且未在正常对照中发现.GJB2基因突变分析发现先证者及家系成员携带有与耳聋相关的235delC、299delAT突变位点.家系内母系成员在发病年龄、听力损失程度和听力曲线上存在较大差异.结论 线粒体tRNAAspA7551G突变可能通过改变对tRNA二级结构的修饰作用,影响tRNA结构的稳定性,最终导致线粒体功能异常,引起耳聋表型,该突变可能是与耳聋相关的线粒体基因新突变.
目的 通過對攜帶線粒體tRNAAsp A7551G突變的母繫遺傳非綜閤徵型耳聾傢繫進行臨床和分子遺傳學特徵分析,探討線粒體tRNAAsp基因突變對非綜閤徵型耳聾的影響.方法 收集1箇攜帶線粒體tRNAAsp A7551G突變的非綜閤徵型耳聾傢繫,對先證者及其傢繫成員進行聽力學檢查、線粒體基因組全序列分析和GJB2基因突變檢測等.結果 傢繫內共6人患病,母繫成員佔4人.先證者線粒體全基因組分析錶明,該線粒體基因組含28箇多態位點,屬于東亞人群A4單體型.其中除A7551G同質性突變外,無其他有功能意義的多態位點.A7551G突變位于線粒體tRNAAsp反密碼子環的反密碼子徬高度保守區的第37位,保守性指數為100％且未在正常對照中髮現.GJB2基因突變分析髮現先證者及傢繫成員攜帶有與耳聾相關的235delC、299delAT突變位點.傢繫內母繫成員在髮病年齡、聽力損失程度和聽力麯線上存在較大差異.結論 線粒體tRNAAspA7551G突變可能通過改變對tRNA二級結構的脩飾作用,影響tRNA結構的穩定性,最終導緻線粒體功能異常,引起耳聾錶型,該突變可能是與耳聾相關的線粒體基因新突變.
목적 통과대휴대선립체tRNAAsp A7551G돌변적모계유전비종합정형이롱가계진행림상화분자유전학특정분석,탐토선립체tRNAAsp기인돌변대비종합정형이롱적영향.방법 수집1개휴대선립체tRNAAsp A7551G돌변적비종합정형이롱가계,대선증자급기가계성원진행은역학검사、선립체기인조전서렬분석화GJB2기인돌변검측등.결과 가계내공6인환병,모계성원점4인.선증자선립체전기인조분석표명,해선립체기인조함28개다태위점,속우동아인군A4단체형.기중제A7551G동질성돌변외,무기타유공능의의적다태위점.A7551G돌변위우선립체tRNAAsp반밀마자배적반밀마자방고도보수구적제37위,보수성지수위100％차미재정상대조중발현.GJB2기인돌변분석발현선증자급가계성원휴대유여이롱상관적235delC、299delAT돌변위점.가계내모계성원재발병년령、은력손실정도화은력곡선상존재교대차이.결론 선립체tRNAAspA7551G돌변가능통과개변대tRNA이급결구적수식작용,영향tRNA결구적은정성,최종도치선립체공능이상,인기이롱표형,해돌변가능시여이롱상관적선립체기인신돌변.
Objective We reported here the clinical and genetic evaluations as well as mutational analysis of mitochondrial DNA (mtDNA) in a Chinese family with maternally transmitted non-syndromic hearing loss and investigated the influence of the mitochondrial tRNAAsp A7551G mutation to the phenotypic manifestation of the deafness.Methods One Chinese Han pedigrees of maternally transmitted nonsyndromic hearing loss were collected.The proband and family members underwent clinical,genetic,and molecular evaluations,such as audiological examinations,mutational analysis of mitochondrial genome and mutational analysis of GJB2 gene.Results Six people of this pedigree suffered from hearing loss,including four matrilineal members,and others did not have significant clinical abnormalities.Sequence analysis of the complete mitochondrial genome in the proband showed that there were 28 mtDNA polymorphisms belonging to East-Asian haplogroup A4.In addition to the A7551G homogeneity mutation,there were no other functionally significant variants found in this family.The A7551 G mutation located immediately at the three prime end to the anticodon,corresponding with the conventional position 37 of tRNAAsp,and its' CI value was 100％ compared with other 15 primate species.The A7551G mutation was absent in other Chinese controls.The mutations on GJB2 were detected by direct sequence analysis,GJB2 235delC and 299delAT which was associated with hearing loss were found in the geneomic DNA of the proband and some matrilineal members.Clinical evaluation showed a variable phenotype of severity,age-at-onset and audiometric configuration of hearing loss in the matrilineal relatives in these families.Conclusions The A7551G mutation may modify the secondary structure of the tRNA,and affect the stabilization of tRNAAsp,produce non-normal functional tRNAAsp ultimately.And it may cause the phenotypic manifestation of the deafness that associated with A7551G mutation.Therefore,the mitochondrial tRNAAsp A7551G mutation may be a new mitochondrial mutation for hearing loss.
