Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T > C
- Author
- Bart Dermaut (UGent) , S Seneca, L Dom, K Smets, L Ceulemans, Joél Smet (UGent) , Boel De Paepe (UGent) , S Tousseyn, S Weckhuysen, M Gewillig, P Pals, P Parizel, Jan De Bleecker (UGent) , Paul Boon (UGent) , L De Meirleir, P De Jonghe, Rudy Van Coster (UGent) , W Van Paesschen and Patrick Santens (UGent)
- Organization
- Abstract
- Background: m. 14487T>C, a missense mutation (p. M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. Objectives: To determine the clinical-neurological spectrum and associated mutation loads in an extended m. 14487T>C family. Methods: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m. 14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Results: Heteroplasmic m. 14487T>C levels (36-52% in leucocytes, 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 leucocytes, 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, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. Interpretation: m. 14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.
- Keywords
- PATIENT, MIGRAINE, MUTATION, COMPLEX-I DEFICIENCY, ND6 GENE
Downloads
-
(...).pdf
- full text
- |
- UGent only
- |
- |
- 481.44 KB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-842229
- MLA
- Dermaut, Bart, et al. “Progressive Myoclonic Epilepsy as an Adult-Onset Manifestation of Leigh Syndrome Due to m.14487T > C.” JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, vol. 81, no. 1, 2010, pp. 90–93, doi:10.1136/jnnp.2008.157354.
- APA
- Dermaut, B., Seneca, S., Dom, L., Smets, K., Ceulemans, L., Smet, J., … Santens, P. (2010). Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T > C. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 81(1), 90–93. https://doi.org/10.1136/jnnp.2008.157354
- Chicago author-date
- Dermaut, Bart, S Seneca, L Dom, K Smets, L Ceulemans, Joél Smet, Boel De Paepe, et al. 2010. “Progressive Myoclonic Epilepsy as an Adult-Onset Manifestation of Leigh Syndrome Due to m.14487T > C.” JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 81 (1): 90–93. https://doi.org/10.1136/jnnp.2008.157354.
- Chicago author-date (all authors)
- Dermaut, Bart, S Seneca, L Dom, K Smets, L Ceulemans, Joél Smet, Boel De Paepe, S Tousseyn, S Weckhuysen, M Gewillig, P Pals, P Parizel, Jan De Bleecker, Paul Boon, L De Meirleir, P De Jonghe, Rudy Van Coster, W Van Paesschen, and Patrick Santens. 2010. “Progressive Myoclonic Epilepsy as an Adult-Onset Manifestation of Leigh Syndrome Due to m.14487T > C.” JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 81 (1): 90–93. doi:10.1136/jnnp.2008.157354.
- Vancouver
- 1.Dermaut B, Seneca S, Dom L, Smets K, Ceulemans L, Smet J, et al. Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T > C. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. 2010;81(1):90–3.
- IEEE
- [1]B. Dermaut et al., “Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T > C,” JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, vol. 81, no. 1, pp. 90–93, 2010.
@article{842229, abstract = {{Background: m. 14487T>C, a missense mutation (p. M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. Objectives: To determine the clinical-neurological spectrum and associated mutation loads in an extended m. 14487T>C family. Methods: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m. 14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Results: Heteroplasmic m. 14487T>C levels (36-52% in leucocytes, 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 leucocytes, 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, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. Interpretation: m. 14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.}}, author = {{Dermaut, Bart and Seneca, S and Dom, L and Smets, K and Ceulemans, L and Smet, Joél and De Paepe, Boel and Tousseyn, S and Weckhuysen, S and Gewillig, M and Pals, P and Parizel, P and De Bleecker, Jan and Boon, Paul and De Meirleir, L and De Jonghe, P and Van Coster, Rudy and Van Paesschen, W and Santens, Patrick}}, issn = {{0022-3050}}, journal = {{JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY}}, keywords = {{PATIENT,MIGRAINE,MUTATION,COMPLEX-I DEFICIENCY,ND6 GENE}}, language = {{eng}}, number = {{1}}, pages = {{90--93}}, title = {{Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T > C}}, url = {{http://doi.org/10.1136/jnnp.2008.157354}}, volume = {{81}}, year = {{2010}}, }
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: