一个琥珀酸半醛脱氢酶缺陷病家系ALDH5A1基因突变分析  

Analysis of ALDH5A1 gene mutation in a Chinese Han family with succinic semiaidehyde dehydrogenasedeficiency

作　　者：姜淑贞[1] 舒剑波[2,3] 张玉琴[2] 范文轩[2] 孟英韬[2,3] 宋力[2,3] 

机构地区：[1]天津医科大学研究生院,300070 [2]天津市儿童医院神经内科 [3]天津市儿科研究所

出　　处：《中华医学遗传学杂志》2013年第4期389-393,共5页Chinese Journal of Medical Genetics

摘　　要：目的对1例临床怀疑且经尿筛查诊断为琥珀酸半醛脱氢酶缺陷病的患儿及家系进行ALDH5A1基因突变分析，以进一步明确诊断和辅助遗传咨询。方法应用聚合酶链反应及DNA直接测序技术对1例琥珀酸半醛脱氢酶缺陷病患儿及其父母的ALDH5A1基因进行突变位点检测，同时检测100名健康对照者的ALDH5A1基因以排除多态性变异。结果患儿携带有ALDH5A1基因编码区序列第3外显子C．527G〉A（P．Glyl76Glu）和第4外显子c．691G〉A（P．Glu231Lys）两种杂合突变，其母亲为c．527G〉A杂合突变携带者，父亲为C．691G〉A杂合突变携带者。另外患儿还存在两种已报道的核酸多态性改变：c．545C〉T杂合突变和c．538C〉T纯合突变。患儿的c．545C〉T突变来源于父亲，c．538C〉T突变分别来源于父母。100名健康对照者中未检测到c．527G〉A和c．691G〉A突变。结论c．527G〉A（P．Glyl76Glu）和c．691G〉A（P．Glu231Lys）错义突变可能是该患儿的致病突变。Objective To detect potential mutation in ALDH5A1 gene for a family affected with suecinic semialdehyde dehydrogenase deficiency diagnosed by clinical inspection and urine screening. Methods Polymerase chain reaction and direct DNA sequencing were carried out for the affected child and her parents. Suspected ALDH5A1 gene mutations were verified in 100 healthy controls to exclude polymorphisms. Results The child was found to have carried 2 heterozygous missense mutations in the coding region ofALDHSA1 gene, namely c. 527G〉 A and c. 691G〉A, for which her mother and father were respectively heterozygotes. The same mutations were not detected in 100 healthy controls. The child was also found to have carried two previously described polymorphisms including a heterozygous c. 545C〉T （derived from her father） and a homozygous c. 538C〉T （derived from her mother）. Conclusion Missense mutations of c. 527G）A and c. 691G〉A in the ALDH5A1 gene are responsible for the pathogenesis of the disease in this family.

关 键 词：琥珀酸半醛脱氢酶缺陷病 琥珀酸半醛脱氢酶 ALDH5A1突变 

分 类 号：R725.9[医药卫生—儿科]