摘要目的 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.

abstractsObjective 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.