摘要目的 分析1个2-羟基戊二酸尿症家系致病基因突变情况,探讨可能引起发病的分子遗传学机制.方法 提取该家系5名成员的外周血基因组DNA,应用PCR技术扩增L2HGDH、D2HGDH和SLC25A13个候选致病基因共28个外显子及其侧翼区序列,扩增产物直接测序确定基因型.结果 DNA测序结果显示,先证者及其发病的胞弟L2HGDH基因第7外显子存在c.845G＞A(p.R282Q)杂合突变,先证者母亲也携带有L2HGDH基因第7外显子c.845G＞A杂合突变;临床表型正常的父亲和胞妹未检测到该突变,因此该突变来自其母亲.本病例家系D2HGDH和SLC25A1两个基因的外显子及其侧翼区序列测序结果未见异常.结论 L2HGDH基因第7外显子c.845G＞A(p.R282Q)突变可能是引起本家系发病的原因.

abstractsObjective To explore pathogenic mutation in a family affected with 2-hydroxyglutaric aciduria.Methods Exons of 3 candidate genes,including L2HGDH,D2HGDH and SLC25A1,were amplified with polymerase chain reaction and subjected to direct sequencing.Results DNA sequencing has found that the proband and his affected younger brother have both carried a heterozygous mutation c.845G＞A (p.R282Q) in the exon 7 of the L2HGDH gene.The same mutation was not detected in the his sister who was healthy.Pedigree analysis has confirmed that the above mutation was inherited from the mother.No mutation was detected in exons and flanking sequences of the D2HGDH and SLC25A1 genes.Conclusion Mutation of the L2HGDH gene probably underlies the 2-hydroxyglutaric aciduria in this family.