中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2012年
2期
121-125
,共5页
陈春燕%张晓梅%汪芳裕%王震凯%朱明%马国建%张元颖%金鑫鑫%施慧%刘炯
陳春燕%張曉梅%汪芳裕%王震凱%硃明%馬國建%張元穎%金鑫鑫%施慧%劉炯
진춘연%장효매%왕방유%왕진개%주명%마국건%장원영%금흠흠%시혜%류형
Peutz-Jeghers综合征%LKB1基因%胚系突变
Peutz-Jeghers綜閤徵%LKB1基因%胚繫突變
Peutz-Jeghers종합정%LKB1기인%배계돌변
Peutz-Jeghers syndrome%LKB1 gene%Germline mutation
目的 研究家族性Peutz-Jeghers综合征患者中LKB1基因胚系突变特征.方法 收集11个Peutz-Jeghers综合征家系,各家系先证者均有典型的黏膜黑斑以及肠道错构瘤性息肉.提取先证者外周血DNA,PCR扩增LKB1基因的9个外显子及其侧翼的部分内含子序列,测序并分析其变异情况和突变性质.收集250名正常人外周血并提取DNA,聚合酶链反应-变性高效液相色谱筛查验证.结果 11个家系先证者中有8例患者LKB1基因外显子及侧翼碱基序列存在杂合性变异,变异类型共9种,包括7种点突变,1种外显子区域小片段碱基缺失以及1种侧翼内含子小片段碱基插入.其中4种考虑为病理性突变,还有4种仅为基因多态性表现,另外有1种变异性质未定.结论 LKB1基因病理性突变是中国人家族性Peutz-Jeghers综合征患者的常见病因,且以点突变为主.
目的 研究傢族性Peutz-Jeghers綜閤徵患者中LKB1基因胚繫突變特徵.方法 收集11箇Peutz-Jeghers綜閤徵傢繫,各傢繫先證者均有典型的黏膜黑斑以及腸道錯構瘤性息肉.提取先證者外週血DNA,PCR擴增LKB1基因的9箇外顯子及其側翼的部分內含子序列,測序併分析其變異情況和突變性質.收集250名正常人外週血併提取DNA,聚閤酶鏈反應-變性高效液相色譜篩查驗證.結果 11箇傢繫先證者中有8例患者LKB1基因外顯子及側翼堿基序列存在雜閤性變異,變異類型共9種,包括7種點突變,1種外顯子區域小片段堿基缺失以及1種側翼內含子小片段堿基插入.其中4種攷慮為病理性突變,還有4種僅為基因多態性錶現,另外有1種變異性質未定.結論 LKB1基因病理性突變是中國人傢族性Peutz-Jeghers綜閤徵患者的常見病因,且以點突變為主.
목적 연구가족성Peutz-Jeghers종합정환자중LKB1기인배계돌변특정.방법 수집11개Peutz-Jeghers종합정가계,각가계선증자균유전형적점막흑반이급장도착구류성식육.제취선증자외주혈DNA,PCR확증LKB1기인적9개외현자급기측익적부분내함자서렬,측서병분석기변이정황화돌변성질.수집250명정상인외주혈병제취DNA,취합매련반응-변성고효액상색보사사험증.결과 11개가계선증자중유8례환자LKB1기인외현자급측익감기서렬존재잡합성변이,변이류형공9충,포괄7충점돌변,1충외현자구역소편단감기결실이급1충측익내함자소편단감기삽입.기중4충고필위병이성돌변,환유4충부위기인다태성표현,령외유1충변이성질미정.결론 LKB1기인병이성돌변시중국인가족성Peutz-Jeghers종합정환자적상견병인,차이점돌변위주.
Objective To screen for potential mutations of LKB1 gene in Chinese familial PeutzJeghers syndrome (PJS) patients and analyze their clinical manifestations.Methods Eleven PJS families were collected and genomic DNA of peripheral blood was extracted.Typically mucosal pigmentation and hamartomatous polyps were present in all 11 probands.Mutation screening of the probands were carried out by PCR and direct sequencing.Two hundred and fifty healthy adults were enrolled as normal controls,for whom genomic DNA of peripheral blood was also extracted. PCR-denaturing high performance liquidchromatography was carried out to verify the mutation identified in the patients.Results Nine germline mutations were identified in eight PJS patients,which included 7 point mutations,1 deletion and 1 insertion.Among these,4 were considered to be pathogenic,of which 2 were de novel,4 were considered to be polymorphism,and 1 was uncertain.Conclusion LKB1 gene mutations with pathogenic effect are a common cause of familial PJS in Chinese patients.Most mutations are point mutations.
