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Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to the m.14487T>C mutation in ND6

Sara Seneca, Bart Dermaut, Patrick Santens UGent, Lina Dom, Katrien Smets, Luc Ceulemans, Joél Smet UGent, Boel De Paepe UGent, Simon Tousseyn and Sarah Weckhuysen, et al. (2009) EUROPEAN JOURNAL OF HUMAN GENETICS. 17(suppl. 1). p.354-354
abstract
Mitochondrial disorders of the oxidative phosphorylation (OXPHOS) system effect ~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 (MT ND), a complex I subunit of the mitochondrial respiratory chain. Thus far it has 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 (8-35% in blood) in adult patients with clinical features including migraine with aura, Leber Hereditary Optic Neuropathy (LHON), sensoneural hearing loss and Diabetes Mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue of these patients. Conclusion: 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.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
in
EUROPEAN JOURNAL OF HUMAN GENETICS
Eur. J. Hum. Genet.
volume
17
issue
suppl. 1
pages
354 - 354
conference name
European Human Genetics conference 2009
conference location
Vienna, Austria
conference start
2009-05-23
conference end
2009-05-26
JCR category
GENETICS & HEREDITY
JCR impact factor
3.564 (2009)
JCR rank
45/142 (2009)
JCR quartile
2 (2009)
ISSN
1018-4813
language
English
UGent publication?
yes
classification
C3
id
990768
handle
http://hdl.handle.net/1854/LU-990768
date created
2010-06-29 11:04:34
date last changed
2015-10-30 09:52:52
@inproceedings{990768,
  abstract     = {Mitochondrial disorders of the oxidative phosphorylation (OXPHOS) system effect {\texttildelow}1/5000 individuals in the general population and present with a surprisingly wide range of multisystemic and neuromuscular phenotypes. The m.14487T{\textrangle}C mutation is a known pathogenic mtDNA mutation resulting in an amino acid substitution (p.M63V) in NADH dehydrogenase 6 (MT ND), a complex I subunit of the mitochondrial respiratory chain. Thus far it has 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{\textrangle}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 (8-35\% in blood) in adult patients with clinical features including migraine with aura, Leber Hereditary Optic Neuropathy (LHON), sensoneural hearing loss and Diabetes Mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue of these patients.
Conclusion: The m.14487T{\textrangle}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.},
  author       = {Seneca, Sara and Dermaut, Bart and Santens, Patrick and Dom, Lina and Smets, Katrien and Ceulemans, Luc and Smet, Jo{\'e}l and De Paepe, Boel and Tousseyn, Simon and Weckhuysen, Sarah and Gewillig, Marc and Pals, Philippe and Parizel, Paul and De Bleecker, Jan and Boon, Paul and De Meirleir, Linda and De Jonghe, Peter and Van Coster, Rudy and Van Paesschen, Wim and Liessens, Willy and Liebaers, Inge},
  booktitle    = {EUROPEAN JOURNAL OF HUMAN GENETICS},
  issn         = {1018-4813},
  language     = {eng},
  location     = {Vienna, Austria},
  number       = {suppl. 1},
  pages        = {354--354},
  title        = {Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to the m.14487T{\textrangle}C mutation in ND6},
  volume       = {17},
  year         = {2009},
}

Chicago
Seneca, Sara, Bart Dermaut, Patrick Santens, Lina Dom, Katrien Smets, Luc Ceulemans, Joél Smet, et al. 2009. “Progressive Myoclonic Epilepsy as an Adult-onset Manifestation of Leigh Syndrome Due to the m.14487T>C Mutation in ND6.” In European Journal of Human Genetics, 17:354–354.
APA
Seneca, S., Dermaut, B., Santens, P., Dom, L., Smets, K., Ceulemans, L., Smet, J., et al. (2009). Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to the m.14487T>C mutation in ND6. EUROPEAN JOURNAL OF HUMAN GENETICS (Vol. 17, pp. 354–354). Presented at the European Human Genetics conference 2009.
Vancouver
1.
Seneca S, Dermaut B, Santens P, Dom L, Smets K, Ceulemans L, et al. Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to the m.14487T>C mutation in ND6. EUROPEAN JOURNAL OF HUMAN GENETICS. 2009. p. 354–354.
MLA
Seneca, Sara, Bart Dermaut, Patrick Santens, et al. “Progressive Myoclonic Epilepsy as an Adult-onset Manifestation of Leigh Syndrome Due to the m.14487T>C Mutation in ND6.” European Journal of Human Genetics. Vol. 17. 2009. 354–354. Print.