中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2010年
5期
429-433
,共5页
王娟%李新明%忻元峰%王丽洁%徐文俊%胡大一
王娟%李新明%忻元峰%王麗潔%徐文俊%鬍大一
왕연%리신명%흔원봉%왕려길%서문준%호대일
心脏缺损,先天性%突变%转录因子
心髒缺損,先天性%突變%轉錄因子
심장결손,선천성%돌변%전록인자
Heart defects,congenital%Mutation%Transcription factors
目的 筛查先天性房间隔缺损相关GATA4基因的新突变.方法 收集85例先天性房间隔缺损患者和200名健康者的临床资料及外周静脉血标本.应用聚合酶链反应扩增GATA4基因的全部外显子,采用双脱氧核苷链末端合成终止法对全部扩增片段进行测序.以BLAST程序将所测序列与GenBank中的已知序列进行比对,以识别基因突变.采用Clustal W软件分析突变氨基酸的保守性.结果 在其中3例先天性房间隔缺损患者的GATA4基因各识别出1个新的杂合错义突变,即第267、354和407位的密码子分别由GTG、ACC和CCA变为ATG、GCC和CAA,亦即c.799G>A、c.1060A>G和c.1220C>A突变,相应地导致第267、354和407位的氨基酸分别由缬氨酸、苏氨酸和脯氨酸变为蛋氨酸、丙氨酸和谷氨酰胺,也称为p.V267M、p.T354A和p.P407Q突变.200名健康对照者均无上述突变.多物种GATA4序列比对显示,第267位的缬氨酸和第407位的脯氨酸在进化上完全保守.结论 在先天性房间隔缺损患者的GATA4基因识别出3个新的杂合错义突变,揭示了先天性房间隔缺损新的分子病因,有助于先天性房间隔缺损的早期防治.
目的 篩查先天性房間隔缺損相關GATA4基因的新突變.方法 收集85例先天性房間隔缺損患者和200名健康者的臨床資料及外週靜脈血標本.應用聚閤酶鏈反應擴增GATA4基因的全部外顯子,採用雙脫氧覈苷鏈末耑閤成終止法對全部擴增片段進行測序.以BLAST程序將所測序列與GenBank中的已知序列進行比對,以識彆基因突變.採用Clustal W軟件分析突變氨基痠的保守性.結果 在其中3例先天性房間隔缺損患者的GATA4基因各識彆齣1箇新的雜閤錯義突變,即第267、354和407位的密碼子分彆由GTG、ACC和CCA變為ATG、GCC和CAA,亦即c.799G>A、c.1060A>G和c.1220C>A突變,相應地導緻第267、354和407位的氨基痠分彆由纈氨痠、囌氨痠和脯氨痠變為蛋氨痠、丙氨痠和穀氨酰胺,也稱為p.V267M、p.T354A和p.P407Q突變.200名健康對照者均無上述突變.多物種GATA4序列比對顯示,第267位的纈氨痠和第407位的脯氨痠在進化上完全保守.結論 在先天性房間隔缺損患者的GATA4基因識彆齣3箇新的雜閤錯義突變,揭示瞭先天性房間隔缺損新的分子病因,有助于先天性房間隔缺損的早期防治.
목적 사사선천성방간격결손상관GATA4기인적신돌변.방법 수집85례선천성방간격결손환자화200명건강자적림상자료급외주정맥혈표본.응용취합매련반응확증GATA4기인적전부외현자,채용쌍탈양핵감련말단합성종지법대전부확증편단진행측서.이BLAST정서장소측서렬여GenBank중적이지서렬진행비대,이식별기인돌변.채용Clustal W연건분석돌변안기산적보수성.결과 재기중3례선천성방간격결손환자적GATA4기인각식별출1개신적잡합착의돌변,즉제267、354화407위적밀마자분별유GTG、ACC화CCA변위ATG、GCC화CAA,역즉c.799G>A、c.1060A>G화c.1220C>A돌변,상응지도치제267、354화407위적안기산분별유힐안산、소안산화포안산변위단안산、병안산화곡안선알,야칭위p.V267M、p.T354A화p.P407Q돌변.200명건강대조자균무상술돌변.다물충GATA4서렬비대현시,제267위적힐안산화제407위적포안산재진화상완전보수.결론 재선천성방간격결손환자적GATA4기인식별출3개신적잡합착의돌변,게시료선천성방간격결손신적분자병인,유조우선천성방간격결손적조기방치.
Objective To screen the gene CATA4 for novel mutations associated with congenital atria] septal defect ( ASD). Methods The clinical data and peripheral venous blood specimen from 85 unrelated subjects with congenital ASD were collected and analyzed in contrast to 200 healthy individuals. The coding exons and the exon/intron boundaries of GATA4 gene were amplified by polymerase chain reaction and sequenced using the di-deoxynucleotide chain termination procedure. The obtained sequences were aligned with those publicized in GenBank with the help of programme BLAST to identify the sequence variations. The software Clustal W was applied to analysis of the conservation of altered amino acids. Results Three novel heterozygous missense GATA4 mutations were identified in 3 of 85 ASD patients, respectively. Namely, the triplet substitutions of ATG for GTG at codon 267, GCC for ACC at codon 354, and CAA for CCA at codon 407, predicting the conversions of valine into methionine at amino acid residue 267 ( V267M) , threonine into alanine at amino acid residue 354 (T354A), and proline into glutamine at amino acid residue 407 (P407Q) , were identified. No mutation was detected in 200 healthy controls. A cross-species alignment of GATA4 encoded protein sequences showed that the valine at amino acid residue 267 and proline at amino acid residue 407 were completely conserved evolutionarily. Conclusion Three novel heterozygous missense GATA4 mutations were identified in patients with congenital ASD, which reveals new molecular etiology responsible for ASD, and contributes to the early prophylaxis and therapy for ASD.