Thymidine phosphorylase gene mutations in patients with mitochondrial neurogastrointestinal encephalomyopathy syndrome.
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| Abstract |
The mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is characterized by the association of gastrointestinal and neurological symptoms. It is a rare autosomal recessive mitochondrial disorder with multiple mitochondrial DNA deletions and/or depletion. It is caused by thymidine phosphorylase (TP) gene mutations resulting in a complete abolition of TP activity. We tested 31 unrelated patients presenting either with a complete MNGIE syndrome (8 patients), a severe intestinal pseudo-obstruction (10 patients), and multiple deletions and/or depletion of mitochondrial DNA (13 patients). All the tested patients presenting with a complete MNGIE had increased thymidine levels in plasma and urine, and no TP activity. The group with pseudo-obstruction syndrome had normal or partial reduction of TP activity. We found pathogenic mutations on TP gene only in the MNGIE syndrome group: all the MNGIE patients were compound heterozygous or homozygous for mutations in the TP gene. Eight of these mutations are yet unreported, confirming the lack of genotype/phenotype correlation in this syndrome. Enzymatic activity and thymidine level are thus rapid diagnosis tests to detect MNGIE affected patients prior to genetic testing for patients with gastrointestinal symptoms.
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| Authors | A Slama, C Lacroix, V Plante-Bordeneuve, A Lombès, M Conti, J M Reimund, E Auxenfants, P Crenn, P Laforêt, A Joannard, D Seguy, H Pillant, P Joly, S Haut, B Messing, G Said, A Legrand, A Guiochon-Mantel |
| Journal | Molecular genetics and metabolism (Mol Genet Metab) Vol. 84 Issue 4 Pg. 326-31 (Apr 2005) ISSN: 1096-7192 [Print] United States |
| PMID | 15781193 (Publication Type: Journal Article) |
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