l‐2‐hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model
AUTOR(ES)
Penderis, Jacques
FONTE
BMJ Group
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2597990Documentos Relacionados
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