Advanced search
1 file | 481.44 KB Add to list

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T > C

Author
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
    • |
    • PDF
    • |
    • 481.44 KB

Citation

Please use this url to cite or link to this publication:

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: