Correlation between genotype, metabolic data, and clinical presentation in carnitine palmitoyltransferase 2 (CPT2) deficiency
| Autor: | Laure Thuillier, Hidayeth Rostane, Veronique Droin, France Demaugre, Michèle Brivet, Noman Kadhom, Carina Prip-Buus, Stéphanie Gobin, Jean-Marie Saudubray, Jean-Paul Bonnefont |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
medicine.medical_specialty Genotype DNA Mutational Analysis Disease Biology medicine.disease_cause Internal medicine Genetics medicine Humans Amino Acid Sequence Beta oxidation Genetics (clinical) chemistry.chemical_classification Mutation Carnitine O-Palmitoyltransferase Sequence Homology Amino Acid Fatty Acids Fatty acid Infant Mitochondrial Myopathies DNA medicine.disease Phenotype Endocrinology chemistry Carnitine palmitoyltransferase II deficiency Oxidation-Reduction Temperature gradient gel electrophoresis |
| Zdroj: | Human mutation. 21(5) |
| ISSN: | 1098-1004 |
| Popis: | Carnitine palmitoyltransferase 2 (CPT2) deficiency, the most common inherited disease of the mitochondrial long-chain fatty acid (LCFA) oxidation, may result in distinct clinical phenotypes, namely a mild adult muscular form and a severe hepatocardiomuscular disease with an onset in the neonatal period or in infancy. In order to understand the mechanisms underlying the difference in severity between these phenotypes, we analyzed a cohort of 20 CPT2-deficient patients being affected either with the infantile (seven patients) or the adult onset form of the disease (13 patients). Using a combination of direct sequencing and denaturing gradient gel electrophoresis, 13 CPT2 mutations were identified, including five novel ones, namely: 371G>A (R124Q), 437A>C (N146T), 481C>T (R161W), 983A>G (D328G), and 1823G>C (D608H). After updating the spectrum of CPT2 mutations (n=39) and genotypes (n=38) as well as their consequences on CPT2 activity and LCFA oxidation, it appears that both the type and location of CPT2 mutations and one or several additional genetic factors to be identified would modulate the LCFA flux and therefore the severity of the disease. |
| Databáze: | OpenAIRE |
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