title: Increased muscle nucleoside levels associated with a novel frameshift mutation in the thymidine phosphorylase gene in a Spanish patient with MNGIE.
abstract: We studied a patient with the cardinal features of mitochondrial gastrointestinal encephalomyopathy (MNGIE). Two of his siblings showed a similar clinical picture. Muscle histochemistry displayed ragged red fibres (RRF) which were COX negative and biochemistry revealed combined defects of complexes III and IV of the mitochondrial respiratory chain. Southern-blot analysis showed multiple mtDNA deletions. Molecular analysis of the ECGF1 gene revealed the presence of a homozygous deletion of 20 base pairs in exon 10, c.1460_1479delGACGGCCCCGCGCTCAGCGG, resulting in a frameshift and synthesis of a protein larger than the wild-type. Thymidine and deoxyuridine accumulation was detected in muscle, indicating loss-of-function of thymidine phosphorylase (TP).
authors.affiliation: Centro de Investigación and Sección de Neuropatología, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Blazquez
authors.forename: M A
authors.initials: MA
authors.lastname: Martín
authors.forename: M C
authors.initials: MC
authors.lastname: Lara
authors.forename: R
authors.initials: R
authors.lastname: Martí
authors.forename: Y
authors.initials: Y
authors.lastname: Campos
authors.forename: A
authors.initials: A
authors.lastname: Cabello
authors.forename: R
authors.initials: R
authors.lastname: Garesse
authors.forename: J
authors.initials: J
authors.lastname: Bautista
authors.forename: A L
authors.initials: AL
authors.lastname: Andreu
authors.forename: J
authors.initials: J
authors.lastname: Arenas
mesh_terms: D015139:Blotting, Southern / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D042967:Electron Transport Complex I; D016368:Frameshift Mutation; D005767:Gastrointestinal Diseases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009705:Nucleosides / Q000378:metabolism*; D013030:Spain; D013939:Thymidine Phosphorylase / Q000235:genetics*
chemical_list: D009097:Multienzyme Complexes; D009705:Nucleosides; D013939:Thymidine Phosphorylase; D042967:Electron Transport Complex I