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
2012年
12期
996-1003
,共8页
彭光华%方芳%郑静%郑斌娇%余啸%伍越%梁玲芝%张琼敏%朱翌%唐霄雯%陈波蓓
彭光華%方芳%鄭靜%鄭斌嬌%餘嘯%伍越%樑玲芝%張瓊敏%硃翌%唐霄雯%陳波蓓
팽광화%방방%정정%정빈교%여소%오월%량령지%장경민%주익%당소문%진파배
听力受损者%DNA,线粒体%RNA,核糖体%突变%氨基糖苷类
聽力受損者%DNA,線粒體%RNA,覈糖體%突變%氨基糖苷類
은력수손자%DNA,선립체%RNA,핵당체%돌변%안기당감류
Hearing impaired persons%DNA,mitochondrial%RNA,ribosomal%Mutation%Aminoglycosides
目的 探讨线粒体12S rRNA基因变异对母系遗传药物性聋表型表达的影响.方法 收集浙江省7所聋校456例非综合征型聋儿资料,提取全血基因组DNA,进行线粒体12S rRNA基因扩增并测序分析.结果 共发现31种已知变异类型,其中1555A＞G的突变率为4.4％ (20/456),可能与耳聋相关的961和1095位点的突变率分别为2.0％(9/456)和0.7％(3/456).1027A＞G、1109T＞C与1431G＞A突变位于12S rRNA基因的高度保守区域且未在449例对照组中发现,可能会增加耳毒性药物的敏感性.1555A＞G突变携带者的临床资料分析发现,不同个体在发病年龄、听力损失程度、听力曲线类型等耳聋表型方面存在差异.结论 线粒体12S rRNA基因是药物性耳聋及非综合征型耳聋相关的突变热点区域.核修饰基因、单体型和环境因素等对耳聋的表型表达有调节作用.
目的 探討線粒體12S rRNA基因變異對母繫遺傳藥物性聾錶型錶達的影響.方法 收集浙江省7所聾校456例非綜閤徵型聾兒資料,提取全血基因組DNA,進行線粒體12S rRNA基因擴增併測序分析.結果 共髮現31種已知變異類型,其中1555A＞G的突變率為4.4％ (20/456),可能與耳聾相關的961和1095位點的突變率分彆為2.0％(9/456)和0.7％(3/456).1027A＞G、1109T＞C與1431G＞A突變位于12S rRNA基因的高度保守區域且未在449例對照組中髮現,可能會增加耳毒性藥物的敏感性.1555A＞G突變攜帶者的臨床資料分析髮現,不同箇體在髮病年齡、聽力損失程度、聽力麯線類型等耳聾錶型方麵存在差異.結論 線粒體12S rRNA基因是藥物性耳聾及非綜閤徵型耳聾相關的突變熱點區域.覈脩飾基因、單體型和環境因素等對耳聾的錶型錶達有調節作用.
목적 탐토선립체12S rRNA기인변이대모계유전약물성롱표형표체적영향.방법 수집절강성7소롱교456례비종합정형롱인자료,제취전혈기인조DNA,진행선립체12S rRNA기인확증병측서분석.결과 공발현31충이지변이류형,기중1555A＞G적돌변솔위4.4％ (20/456),가능여이롱상관적961화1095위점적돌변솔분별위2.0％(9/456)화0.7％(3/456).1027A＞G、1109T＞C여1431G＞A돌변위우12S rRNA기인적고도보수구역차미재449례대조조중발현,가능회증가이독성약물적민감성.1555A＞G돌변휴대자적림상자료분석발현,불동개체재발병년령、은력손실정도、은력곡선류형등이롱표형방면존재차이.결론 선립체12S rRNA기인시약물성이롱급비종합정형이롱상관적돌변열점구역.핵수식기인、단체형화배경인소등대이롱적표형표체유조절작용.
Objective To investigate mutational spectrum and frequency of the mitochondrial 12S rRNA gene in Chinese subjects with aminoglycoside-induced and non-syndromic hearing loss.Methods Total of 456 subjects with non-syndromic hearing loss were recruited from seven schools for deaf-mutes in Zhejiang province.Genomic DNA was extracted from the whole blood,and then the DNA fragment was amplified spanning the 12S rRNA gene,followed by sequencing and analyzed.Results Thirty-one variants were identified by mutation analysis of 12S rRNA gene in these subjects.The frequency of the known 1555A ＞ G mutation was 4.4％ (20/456).Prevalence of other putative deafness-associated mutation at positions 961 and 1095 were 2.0％ (9/456) and 0.7％ (3/456) respectively.Furthermore,the 1027A ＞ G,1109T ＞ C and 1431G＞A variants conferred increased sensitivity to ototoxic drugs or non-syndromic deafness as they were absent in 449 Chinese controls and localized at highly conserved nucleotides of this 12S rRNA gene.Moreover,clinical data showed a wide range of age-of-onset,variety of severity and various audiometric configurations in subjects carrying the 1555A＞G mutation.Conclusions Our data demonstrated that the mitochondrial 12S rRNA gene is the hot spot for mutations associated with aminoglycoside ototoxicity and non-syndromic hearing loss.Nuclear modifier genes,mitochondrial haplotypes and environmental factors might play a role in the phenotypic manifestation of these mutations.
