Evidence for Genetic Heterogeneity in D-2-Hydroxyglutaric Aciduria
Evidence for Genetic Heterogeneity in D-2-Hydroxyglutaric Aciduria
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DOI：
10.1002/humu.21186
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发表时间：
2010-03-01
期刊：
影响因子：
3.9
通讯作者：
Salomons, Gajja S.
中科院分区：
文献类型：
--
作者：
Kranendijk, Martijn;Struys, Eduard A.;Salomons, Gajja S.
我们对50例d -2-羟基戊二酸尿症（D-2-HGA）患者进行了分子、酶和代谢研究，这些患者在生理体液中积累了d -2-羟基戊二酸（D-2-HG）。50例患者中有24例检测到d -2-羟基戊二酸脱氢酶（D2HGDH）基因的推定致病性突变，该基因编码d -2-羟基戊二酸脱氢酶（D-2-HGDH）。D-2-HGDH的酶分析证实，所有突变患者的酶活性都受损，而酶活性正常的D-2-HGA患者没有突变。D-2-HGA突变阳性患者的体液中D-2-HG浓度明显低于突变阴性患者。这些结果表明，多个遗传位点可能与D-2-HG的高排泄有关。因此，我们建议一种新的分类：D-2-HGA I型与D-2-HGDH缺乏相关，而特发性D-2-HGA表现为与I型患者相比，D-2-HGDH活性正常，体液中D-2-HG水平较高。在未来的研究中，仍有可能揭示具有不同基因位点的特发性D-2-HGA患者的几种分类。[j] .科学通报，2010。(C) 2009 Wiley-Liss, Inc。
We performed molecular, enzyme, and metabolic studies in 50 patients with D-2-hydroxyglutaric aciduria (D-2-HGA) who accumulated D-2-hydroxyglutarate (D-2-HG) in physiological fluids. Presumed pathogenic mutations were detected in 24 of 50 patients in the D-2-hydroxyglutarate dehydrogenase (D2HGDH) gene, which encodes D-2-hydroxyglutarate dehydrogenase (D-2-HGDH). Enzyme assay Of D-2-HGDH confirmed that all patients with mutations had impaired enzyme activity, whereas patients with D-2-HGA whose enzyme activity was normal did not have mutations. Significantly lower D-2-HG concentrations in body fluids were observed in mutation-positive D-2-HGA patients than in mutation-negative patients. These results imply that multiple genetic loci may be associated with hyperexcretion of D-2-HG. Accordingly, we suggest a new classification: D-2-HGA Type I associates with D-2-HGDH deficiency, whereas idiopathic D-2-HGA manifests with normal D-2-HGDH activity and higher D-2-HG levels in body fluids compared with Type I patients. It remains possible that several classifications for idiopathic D-2-HGA patients with diverse genetic loci will be revealed in future studies. Hum Mutat 31:279-283, 2010. (C) 2009 Wiley-Liss, Inc.