L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model
L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model
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DOI：
10.1136/jmg.2006.042507
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发表时间：
2007-05-01
影响因子：
4
通讯作者：
Mellersh, Cathryn S.
中科院分区：
文献类型：
--
作者：
Penderis, Jacques;Calvin, Jacqui;Mellersh, Cathryn S.
L-2-羟基戊二酸尿症 (L-2-HGA) 是一种神经代谢紊乱，可产生多种临床神经功能缺损，包括精神运动迟缓、癫痫发作和共济失调。 L-2-HGA 的生化特征是 L-2-羟基戊二酸 (L-2-HG) 在脑脊液、血浆和尿液中的积累。最近显示，编码 L-2-羟基戊二酸脱氢酶的染色体 14q22 上的基因 L2HGDH（Entrez 基因 ID 79944）内的突变可导致人类产生 L-2-HGA。在分离 L-2-HGA 的远交宠物狗群体中使用候选基因方法，在 L2HGDH 的犬同源物中鉴定出致病分子缺陷并进行了表征。 DNA 测序和谱系分析表明犬模型中存在共同的奠基者效应。犬模型与人类疾病的许多临床和 MRI 特征相同，并且作为 L-2-HGA 自发模型代表了宝贵的资源。
L-2-hydroxyglutaric aciduria (L-2-HGA) is a neurometabolic disorder that produces a variety of clinical neurological deficits, including psychomotor retardation, seizures and ataxia. The biochemical hallmark of L-2-HGA is the accumulation of L-2-hydroxyglutaric acid (L-2-HG) in cerebrospinal fluid, plasma and urine. Mutations within the gene L2HGDH (Entrez Gene ID 79944) on chromosome 14q22 encoding L-2-hydroxyglutaric acid dehydrogenase have recently been shown to cause L-2-HGA in humans. Using a candidate gene approach in an outbred pet dog population segregating L-2-HGA, the causal molecular defect was identified in the canine homologue of L2HGDH and characterised. DNA sequencing and pedigree analysis indicate a common founder effect in the canine model. The canine model shares many of the clinical and MRI features of the disease in humans and represents a valuable resource as a spontaneous model of L-2-HGA.