中华儿科杂志
中華兒科雜誌
중화인과잡지
Chinese Journal of Pediatrics
2013年
10期
783-786
,共4页
舒剑波%张玉琴%姜淑贞%张春花%孟英韬%王洪%宋力
舒劍波%張玉琴%薑淑貞%張春花%孟英韜%王洪%宋力
서검파%장옥금%강숙정%장춘화%맹영도%왕홍%송력
氨基酸代谢障碍,先天性%2甲基3羟基丁酰辅酶 A脱氢酶缺陷症%乙酰乙酰辅酶A硫解酶缺陷症%ACAT1基因%HADH2基因%尿代谢谱分析
氨基痠代謝障礙,先天性%2甲基3羥基丁酰輔酶 A脫氫酶缺陷癥%乙酰乙酰輔酶A硫解酶缺陷癥%ACAT1基因%HADH2基因%尿代謝譜分析
안기산대사장애,선천성%2갑기3간기정선보매 A탈경매결함증%을선을선보매A류해매결함증%ACAT1기인%HADH2기인%뇨대사보분석
Amino acid metabolism,inborn errors%2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency%2-methylacetoacetyl-CoA thiolase deficiency%ACAT1%HADH2%Urinary metabolites profile analysis
目的 对一个2甲基3羟基丁酰辅酶A脱氢酶缺陷症(MHBDD)家系进行基因突变分析,为疾病的诊断及遗传咨询提供依据.方法 采集患儿及父母外周静脉血,分别提取总RNA及基因组DNA.应用RT-PCR方法扩增ACAT1基因全编码区序列.应用PCR方法扩增ACAT1基因启动子序列及HADH2基因全部外显子编码区及两侧内含子区域.所有扩增产物,均进行直接测序并与参考序列进行比对.结果 患儿1岁1个月,主要表现为精神运动发育迟缓,就诊时尚不能独站,生化检测血乳酸升高(3.19 mmol/L),头颅核磁提示髓鞘发育延迟,气相色谱质谱检测提示乙酰乙酰辅酶A硫解酶缺陷症.ACAT1基因全编码区及启动子区域未见异常突变位点,HADH2基因第4外显子发生c.388C ＞T(p.R130C)半合子改变,使编码的第130位精氨酸变成了半胱氨酸.患者母亲该位点为杂合改变,父亲正常.结论 通过基因突变分析确诊了1例2甲基3羟基丁酰辅酶A脱氢酶缺陷症患儿,p.R130C是该患儿的致病突变,为准确的遗传咨询提供了可能.
目的 對一箇2甲基3羥基丁酰輔酶A脫氫酶缺陷癥(MHBDD)傢繫進行基因突變分析,為疾病的診斷及遺傳咨詢提供依據.方法 採集患兒及父母外週靜脈血,分彆提取總RNA及基因組DNA.應用RT-PCR方法擴增ACAT1基因全編碼區序列.應用PCR方法擴增ACAT1基因啟動子序列及HADH2基因全部外顯子編碼區及兩側內含子區域.所有擴增產物,均進行直接測序併與參攷序列進行比對.結果 患兒1歲1箇月,主要錶現為精神運動髮育遲緩,就診時尚不能獨站,生化檢測血乳痠升高(3.19 mmol/L),頭顱覈磁提示髓鞘髮育延遲,氣相色譜質譜檢測提示乙酰乙酰輔酶A硫解酶缺陷癥.ACAT1基因全編碼區及啟動子區域未見異常突變位點,HADH2基因第4外顯子髮生c.388C ＞T(p.R130C)半閤子改變,使編碼的第130位精氨痠變成瞭半胱氨痠.患者母親該位點為雜閤改變,父親正常.結論 通過基因突變分析確診瞭1例2甲基3羥基丁酰輔酶A脫氫酶缺陷癥患兒,p.R130C是該患兒的緻病突變,為準確的遺傳咨詢提供瞭可能.
목적 대일개2갑기3간기정선보매A탈경매결함증(MHBDD)가계진행기인돌변분석,위질병적진단급유전자순제공의거.방법 채집환인급부모외주정맥혈,분별제취총RNA급기인조DNA.응용RT-PCR방법확증ACAT1기인전편마구서렬.응용PCR방법확증ACAT1기인계동자서렬급HADH2기인전부외현자편마구급량측내함자구역.소유확증산물,균진행직접측서병여삼고서렬진행비대.결과 환인1세1개월,주요표현위정신운동발육지완,취진시상불능독참,생화검측혈유산승고(3.19 mmol/L),두로핵자제시수초발육연지,기상색보질보검측제시을선을선보매A류해매결함증.ACAT1기인전편마구급계동자구역미견이상돌변위점,HADH2기인제4외현자발생c.388C ＞T(p.R130C)반합자개변,사편마적제130위정안산변성료반광안산.환자모친해위점위잡합개변,부친정상.결론 통과기인돌변분석학진료1례2갑기3간기정선보매A탈경매결함증환인,p.R130C시해환인적치병돌변,위준학적유전자순제공료가능.
Objective The aim of this study was to explore the genetic features of a family with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (MHBDD) which may provide the basis for the diagnosis and genetic counseling.Method Clinical data of the proband was collected,total RNA and genomic DNA were extracted from the peripheral blood.The whole coding region of the ACAT1 gene was amplified by RT-PCR.5' noncoding region of the ACAT1 gene and all 6 exons and flanking intron regions of the HADH2 gene were amplified by PCR.All amplification products were directly sequenced and compared with the reference sequence.Result (1) The patient was a one-year-old boy who presented with psychomotor retardation and astasia when he was admitted to the hospital.Biochemical test revealed slight hyperlactatemia (3.19 mmol/L)and magnetic resonance imaging showed delayed myelination.2-Methylacetoacetyl-CoA thiolase deficiency was suggested by gas chromatography-mass spectrometry.(2) There was no mutation in the ACAT1 gene and a hemizygous missense mutation c.388C ＞ T was found in the 4 exon of the HADH2 gene which resulted in p.R130C.Proband's mother was the heterozygote and the father was normal.Conclusion This is the first report on MHBDD patient and HADH2 mutation in China.p.R130C is responsible for the pathogenesis of the discase in the infant.
