| Autor: |
Seneca, Sara, Dermaut, Bart, Santens, P., Dom, L., Smets, K., Ceulemans, L., Smet, Joél, De Paepe, Boél, Tousseyn, S., Weckhuyssen, Sarah, Pals, Philippe, Parizel, Paul, De Bleecker, J., Boon, Paul, De Meirleir, Linda, De Jonghe, P., Van Coster, Rudy, Van Paesschen, W., Lissens, Willy, Liebaers, Ingeborg |
| Přispěvatelé: |
Department of Embryology and Genetics, Pediatrics, Reproduction and Genetics |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
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| Popis: |
Mitochondrial disorders of oxidative phosphorylation (OXPHOS disorders) affect ~1/5000 individuals in the general population and present with a surprisingly wide range of multisystemic and neuromuscular phenotypes. The m.14487T>C mutation is a known pathogenic mtDNA mutation resulting in an amino acid substitution (p.M63V) in NADH dehydrogenase 6 (ND6), a complex I subunit of the mitochondrial respiratory chain, and has thus far been found in isolated cases with infantile Leigh syndrome and progressive dystonia. We report here adult and late-onset phenotypes as it was seen in a 5-generation Belgian family with 12 affected family members. Clinical and mutation load data were available for 9 family members, while biochemical analysis of the respiratory chain was performed in 3 muscle biopsies. Heteroplasmic m.14487T>C levels (36-52 % in leukocytes, 97-99 % in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100 % in leukocytes, 100 % in muscle). We found lower mutation loads (between 8 and 35 % in blood) in adult patients with clinical features including migraine with aura, Leber Hereditary Optic Neuropathy (LHON), sensorineural hearing loss and Diabetes Mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. Conclusions: The m.14487T>C mutation resulted in a broad spectrum of phenotypes in our family. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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