Increased muscle nucleoside levels associated with a novel frameshift mutation in the thymidine phosphorylase gene in a Spanish patient with MNGIE.
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).
Blazquez
A
A
Centro de Investigación and Sección de Neuropatología, Hospital Universitario 12 de Octubre, Madrid, Spain.
Martín
M A
MA
Lara
M C
MC
Martí
R
R
Campos
Y
Y
Cabello
A
A
Garesse
R
R
Bautista
J
J
Andreu
A L
AL
Arenas
J
J
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*
D009097:Multienzyme Complexes; D009705:Nucleosides; D013939:Thymidine Phosphorylase; D042967:Electron Transport Complex I