L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. Issue 5 (2nd May 2007)

• Record Type: Journal Article
• Authors: Penderis, Jacques; Calvin, Jacqui; Abramson, Carley; Jakobs, Cornelis; Pettitt, Louise; Binns, Matthew M; Verhoeven, Nanda M; O'Driscoll, Eamonn; Platt, Simon R; Mellersh, Cathryn S
• Is Part Of: Journal of medical genetics. Volume 44:Issue 5(2007)
• Page Start: 334
• Page End: 340
• Publication Date: 2007-05-02
• Subjects: GC, gas chromatography -- l-2-HG, l-2-hydroxyglutaric acid -- l-2-HGA, l-2-hydroxyglutaric aciduria; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2006.042507
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : 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.