中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2011年
5期
485-489
,共5页
常染色体显性成人多囊肾病%PKD1基因%PKD2基因%新生突变
常染色體顯性成人多囊腎病%PKD1基因%PKD2基因%新生突變
상염색체현성성인다낭신병%PKD1기인%PKD2기인%신생돌변
autosomal dominant polycystic kidney disease%PKD1 gene%PKD2 gene%de novo mutation
目的 鉴定两个常染色体显性成人多囊肾病家系的致病突变.方法 采用酚氯仿法提取家系成员及无亲缘关系的100名健康对照个体的外周血白细胞DNA,PCR扩增先证者致病基因PKD1、PKD2的所有外显子序列及其侧翼内含子剪切区域,直接测序确定DNA序列的变异.通过家系和正常对照的比较分析,对检测到的变异是否与疾病相关进行了初步探讨.结果 在两个家系中共检测到5个序列变异:PKD1:c.2469G＞A,PKD1:c.5014_5015 delAG,PKD1:c.10529C＞T,PKD2:c.568G＞A和PKD2:c.2020-1_2020 delAG.其中PKD1:c.2469G＞A和PKD2:c.2020-1_2020 delAG为新发现的变异.此外,检测到的移码突变和剪切突变未见于家系中健康成员及无亲缘关系的正常对照.结论 PKD1:c.5014_5015 delAG和PKD2:c.2020-1_2020 delAG分别为家系A和B的致病突变,且PKD2:c.2020-1_2020 delAG为先证者新发生的突变.
目的 鑒定兩箇常染色體顯性成人多囊腎病傢繫的緻病突變.方法 採用酚氯倣法提取傢繫成員及無親緣關繫的100名健康對照箇體的外週血白細胞DNA,PCR擴增先證者緻病基因PKD1、PKD2的所有外顯子序列及其側翼內含子剪切區域,直接測序確定DNA序列的變異.通過傢繫和正常對照的比較分析,對檢測到的變異是否與疾病相關進行瞭初步探討.結果 在兩箇傢繫中共檢測到5箇序列變異:PKD1:c.2469G＞A,PKD1:c.5014_5015 delAG,PKD1:c.10529C＞T,PKD2:c.568G＞A和PKD2:c.2020-1_2020 delAG.其中PKD1:c.2469G＞A和PKD2:c.2020-1_2020 delAG為新髮現的變異.此外,檢測到的移碼突變和剪切突變未見于傢繫中健康成員及無親緣關繫的正常對照.結論 PKD1:c.5014_5015 delAG和PKD2:c.2020-1_2020 delAG分彆為傢繫A和B的緻病突變,且PKD2:c.2020-1_2020 delAG為先證者新髮生的突變.
목적 감정량개상염색체현성성인다낭신병가계적치병돌변.방법 채용분록방법제취가계성원급무친연관계적100명건강대조개체적외주혈백세포DNA,PCR확증선증자치병기인PKD1、PKD2적소유외현자서렬급기측익내함자전절구역,직접측서학정DNA서렬적변이.통과가계화정상대조적비교분석,대검측도적변이시부여질병상관진행료초보탐토.결과 재량개가계중공검측도5개서렬변이:PKD1:c.2469G＞A,PKD1:c.5014_5015 delAG,PKD1:c.10529C＞T,PKD2:c.568G＞A화PKD2:c.2020-1_2020 delAG.기중PKD1:c.2469G＞A화PKD2:c.2020-1_2020 delAG위신발현적변이.차외,검측도적이마돌변화전절돌변미견우가계중건강성원급무친연관계적정상대조.결론 PKD1:c.5014_5015 delAG화PKD2:c.2020-1_2020 delAG분별위가계A화B적치병돌변,차PKD2:c.2020-1_2020 delAG위선증자신발생적돌변.
Objective To identify the responsible mutation of autosomal dominant polycystic kidney disease (ADPKD) in two Chinese families.Methods Total genomic DNA of all available family members and 100 unrelated healthy controls was extracted from peripheral blood leukocytes using a standard phenol-chloroform procedure. All exons with intronic flanking sequences of the PKD1 and PKD2 genes in the probands were amplified by PCR.Mutations were detected directly by DNA sequencing.To evaluate the pathogenicity of the variations,family and control based analyses were performed.Results Five sequence variants were identified in the two families including PKD1:c.2469G＞A,PKD1:c.5014_5015delAG,PKD1:c.10529C＞T,PKD2:c.568G＞A and PKD2:c.2020-1_2020delAG.Among them,PKD1:c.2469G＞ A and PKD2:c.2020-1 _ 2020 delAG were novel mutations. Furthermore,the frameshift and splicing site mutations detected in the affected individuals were not detected in their unaffected relatives and 100 unrelated normal controls.Conclusion PKD1:c.5014_5015delAG and PKD2:c.2020-1_2020delAG are the responsible mutations of family A and B,respectively,and PKD2:c.2020-1_2020delAG is a de novo mutation.
