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    ABSTRACT: While mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is typically associated with mutations in the nuclear gene encoding for thymidine phosphorylase (ECGF1, TYMP), a similar clinical phenotype was described in patients carrying mutations in the nuclear-encoded polymerase gamma (POLG1) as well as a few mitochondrial tRNA genes. Here we report a novel mutation in the mitochondrial tRNA(Val) (MTTV) gene in a girl presenting with clinical symptoms of MNGIE-like gastrointestinal dysmotility and cachexia. Clinical, histological, biochemical and single cell investigations were performed. The heteroplasmic m.1630A>G mutation was detected in the mitochondrial tRNA(Val) (MTTV) gene in the patient's muscle, blood leukocytes and myoblasts, as well as in blood DNA of the unaffected mother. We provide clinical, biochemical, histological, and molecular genetic evidence on the single cell level for the pathogenicity of this mutation. Our finding adds to the genetic heterogeneity of MNGIE-like gastrointestinal symptoms and highlights the importance of a thorough genetic workup in case of suspected mitochondrial disease.
    Journal of Neurology 03/2009; 256(5):810-5. · 3.58 Impact Factor
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    ABSTRACT: Although the (13)C-octanoic acid breath test (OBT) has been applied to diabetic patients for assessing gastric emptying, such studies are still limited. Gastric emptying was measured using solid meal containing (13)C-octanoic acid in 52 patients with Type 2 diabetes mellitus and 4 diabetic patients with mitochondrial DNA (mitDNA) 3243 mutation. Delayed gastric emptying was detected in 29% of patients with Type 2 diabetes mellitus, and multiple regression analysis showed that gastric emptying was independently associated with gastrointestinal symptoms and cardiac autonomic neuropathy. Gastric emptying was not related to gastric dysrhythmia in cutaneous electrogastrography (EGG). Diabetic patients with mitDNA 3243 mutation showed delayed gastric emptying. Because the pathogenesis of delayed gastric emptying is multifactorial in diabetic patients, the recently developed OBT is useful for studying gastric emptying in various clinical settings of diabetic patients.
    Journal of Diabetes and its Complications 01/2006; 20(5):295-301. · 2.06 Impact Factor
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    ABSTRACT: To report on a family with five members who carry the A3243G mutation in mitochondrial tRNA for leucine 1 (MTTL1) and present with diabetes, chronic intestinal pseudo-obstruction (CIPO) and recurrent pancreatitis, and to screen for this mutation in a cohort of 36 unrelated patients with recurrent pancreatitis. The mutation was quantified in several tissue samples from patients. Respiratory chain activity was studied in muscle biopsies and fibroblast cultures. In addition, the thymidine phosphorylase gene (TP) involved in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and three genes involved in chronic pancreatitis - PRSS1, SPINK1 and CFTR - were sequenced in affected patients. Finally, the MTTL1 gene was examined in 36 unrelated patients who had recurrent pancreatitis, but no mutations in the PRSS1 and SPINK1 genes. Heteroplasmy for the mtDNA A3243G mutation was found in all tissue samples from these patients, but no mutations were found in the genes coding for thymidine phosphorylase, PRSS1, SPINK1 and CFTR. Also, none of the 36 unrelated patients with recurrent pancreatitis were carrying any MTTL1 mutations. The mtDNA A3243G mutation associated with the gastrointestinal manifestations observed in the affected family should be regarded as a possible cause of CIPO and unexplained recurrent pancreatitis. However, the mutation is probably only weakly involved in cases of isolated recurrent pancreatitis.
    Diabetes & Metabolism 11/2008; 34(6 Pt 1):620-6. · 2.39 Impact Factor

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