T2基因突变致3-酮硫解酶缺乏症

3-ketothiolase deficiency induced by T2 gene mutation

摘要:

目的：在非糖尿病性酮症酸中毒病例中寻找3-酮硫解酶（3-ketothiolase，3KT）（以下简称T2）基因异常情况，进一步为3KT缺乏症（3-ketothiolase deficiency，3KTD）的诊断提供依据，揭示T2在异亮氨酸代谢过程中的作用，并探讨基因突变导致该疾病的潜在机制。方法：采集先证者及家属外周血，同时采集50例正常儿童外周血为正常对照，提取外周血DNA，用PCR法扩增T2基因全部外显子及其侧翼，对扩增产物进行直接测序，检测突变位点。结果：先证者外显子5第46位C突变为T，该突变导致T2蛋白第127位氨基酸由丙氨酸突变为缬氨酸，先证者父母、哥哥及正常对照组该位点均未见突变；先证者外显子1、内含子5、内含子8发现多个单核苷酸多态性（single-nucleotide polymorphism，SNP）。结论：T2基因外显子5 A127V，可能是3KTD的潜在病因。

Abstract:

Objective：To research the gene mutation of 3-ketothiolase（3KT）（T2） in non-diabetic ketoacidosis，to provide references for diagnosis of 3-ketothiolase deficiency（3KTD），to reveal the role of T2 in isoleucine metabolism and to explore potential mecha－nisms of 3KTD by gene mutations. Methods：DNA was extracted from peripheral blood of the patients，his family members and healthy children. The entire coding regions of T2 gene with flanking intronic regions were amplified by PCR and the amplified products were directly sequenced and mutation sites were detected. Results：A127V missense mutation in exon 5 was identified in proband and no mutation was observed in other tests. Some single nucleotide polymorphisms（SNPs） of T2 gene were detected. Conclusion：A127V in exon 5 of T2 gene may be a potential pathogenesis of 3KTD.