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
3期
261-265
,共5页
曾敏慧%邱文娟%顾学范%王瑜%周建德%叶军%韩连书%张惠文
曾敏慧%邱文娟%顧學範%王瑜%週建德%葉軍%韓連書%張惠文
증민혜%구문연%고학범%왕유%주건덕%협군%한련서%장혜문
糖原累积病Ⅱ型%酸性-α-葡萄糖苷酶%产前诊断%假性缺陷等位基因
糖原纍積病Ⅱ型%痠性-α-葡萄糖苷酶%產前診斷%假性缺陷等位基因
당원루적병Ⅱ형%산성-α-포도당감매%산전진단%가성결함등위기인
glycogen storage disease type Ⅱ%acid-alpha-glucosidase%prenatal diagnosis%pseudodeficiency allele
目的 为1个糖原累积病Ⅱ型(glycogen storage disease typeⅡ,GSDⅡ)家系进行酶学和产前基因诊断.方法 用酸性-α-葡萄糖苷酶(acid-alpha-glucosidase,GAA)特异性水解荧光底物4-甲基伞型酮-α-D-吡喃葡萄糖苷(4-methylumbelliferyl-α-D-glucopyranoside,4-MUG)和阿卡波糖抑制其同工酶的方法检测外周血白细胞和羊水细胞GAA酶活性,聚合酶链反应扩增GAA基因外显子编码区序列,直接测序分析GAA基因突变情况.结果 先证者外周血白细胞与胎儿羊水细胞GAA酶活性均明显低于正常参考值范围,分别为正常对照平均值的12.3% 和1.1%.先证者和胎儿均携带新无义突变 p.W738X 和已报道的无义突变p.E888X;先证者、母亲和胎儿均携带假性缺陷等位基因[c.1726G>A; c.2065G>A].结论 通过GAA酶活性检测结合GAA基因分析对1个GSDⅡ家系进行了产前诊断.由于假性缺陷等位基因可引起GAA酶活性降低,故GAA基因分析应作为亚洲人群GSDⅡ产前诊断的常规手段.
目的 為1箇糖原纍積病Ⅱ型(glycogen storage disease typeⅡ,GSDⅡ)傢繫進行酶學和產前基因診斷.方法 用痠性-α-葡萄糖苷酶(acid-alpha-glucosidase,GAA)特異性水解熒光底物4-甲基傘型酮-α-D-吡喃葡萄糖苷(4-methylumbelliferyl-α-D-glucopyranoside,4-MUG)和阿卡波糖抑製其同工酶的方法檢測外週血白細胞和羊水細胞GAA酶活性,聚閤酶鏈反應擴增GAA基因外顯子編碼區序列,直接測序分析GAA基因突變情況.結果 先證者外週血白細胞與胎兒羊水細胞GAA酶活性均明顯低于正常參攷值範圍,分彆為正常對照平均值的12.3% 和1.1%.先證者和胎兒均攜帶新無義突變 p.W738X 和已報道的無義突變p.E888X;先證者、母親和胎兒均攜帶假性缺陷等位基因[c.1726G>A; c.2065G>A].結論 通過GAA酶活性檢測結閤GAA基因分析對1箇GSDⅡ傢繫進行瞭產前診斷.由于假性缺陷等位基因可引起GAA酶活性降低,故GAA基因分析應作為亞洲人群GSDⅡ產前診斷的常規手段.
목적 위1개당원루적병Ⅱ형(glycogen storage disease typeⅡ,GSDⅡ)가계진행매학화산전기인진단.방법 용산성-α-포도당감매(acid-alpha-glucosidase,GAA)특이성수해형광저물4-갑기산형동-α-D-필남포도당감(4-methylumbelliferyl-α-D-glucopyranoside,4-MUG)화아잡파당억제기동공매적방법검측외주혈백세포화양수세포GAA매활성,취합매련반응확증GAA기인외현자편마구서렬,직접측서분석GAA기인돌변정황.결과 선증자외주혈백세포여태인양수세포GAA매활성균명현저우정상삼고치범위,분별위정상대조평균치적12.3% 화1.1%.선증자화태인균휴대신무의돌변 p.W738X 화이보도적무의돌변p.E888X;선증자、모친화태인균휴대가성결함등위기인[c.1726G>A; c.2065G>A].결론 통과GAA매활성검측결합GAA기인분석대1개GSDⅡ가계진행료산전진단.유우가성결함등위기인가인기GAA매활성강저,고GAA기인분석응작위아주인군GSDⅡ산전진단적상규수단.
Objective To carry out prenatal diagnosis for a glycogen storage disease typeⅡ(GSDⅡ) affected family. Methods The acid-α-glucosidase (GAA) activity was measured in whole leukocytes and cultured amniocytes with 4-methylumbelliferyl-α-D-glucopyranoside as substrate and with acarbose as inhibitor. The coding regions of GAA gene were amplified by polymerase chain reaction and analyzed by direct DNA sequencing. Results The proband and the fetus had low GAA activity (12.3% and 1.1% of the average normal range, respectively). Mutation analysis of the GAA gene revealed a novel nonsense mutation p.W738X and a reported nonsense mutation p.E888X in both the proband and the fetus; the reported pseudodeficiency allele c.[1726G>A;2065G>A] was found in the proband, the mother and the fetus. Conclusion The proband and the fetus were both GSDⅡaffected. A combination of GAA activity analysis and mutation analysis is efficient for the prenatal diagnosis of GSDⅡ. Mutation analysis should be a routine method in the prenatal diagnosis of GSDⅡ in Asian population, where pseudodeficiency allele can cause low GAA activity in normal individuals which is relatively common in Asian.
