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

Bart Dermaut UGent, S Seneca, L Dom, K Smets, L Ceulemans, Joél Smet UGent, Boel De Paepe UGent, S Tousseyn, S Weckhuysen and M Gewillig, et al. (2010) JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. 81(1). p.90-93
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PATIENT, MIGRAINE, MUTATION, COMPLEX-I DEFICIENCY, ND6 GENE
journal title
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
J. Neurol. Neurosurg. Psychiatry
volume
81
issue
1
pages
90 - 93
Web of Science type
Article
Web of Science id
000272855400022
JCR category
SURGERY
JCR impact factor
4.791 (2010)
JCR rank
4/186 (2010)
JCR quartile
1 (2010)
ISSN
0022-3050
DOI
10.1136/jnnp.2008.157354
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
842229
handle
http://hdl.handle.net/1854/LU-842229
date created
2010-01-27 11:07:36
date last changed
2013-05-13 15:49:27
@article{842229,
  abstract     = {Background: m. 14487T{\textrangle}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{\textrangle}C family.
Methods: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m. 14487T{\textrangle}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{\textrangle}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{\textrangle}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, Jo{\'e}l 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},
  keyword      = {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 {\textrangle} C},
  url          = {http://dx.doi.org/10.1136/jnnp.2008.157354},
  volume       = {81},
  year         = {2010},
}

Chicago
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.
APA
Dermaut, B., Seneca, S., Dom, L., Smets, K., Ceulemans, L., Smet, J., De Paepe, B., 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.
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.
MLA
Dermaut, Bart, S Seneca, L Dom, et al. “Progressive Myoclonic Epilepsy as an Adult-onset Manifestation of Leigh Syndrome Due to m.14487T > C.” JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 81.1 (2010): 90–93. Print.