Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA) (original) (raw)
Leigh syndrome caused by mutations in the flavoprotein (Fp) subunit of succinate dehydrogenase (SDHA)
- R Horváth1,
- A Abicht2,
- E Holinski-Feder4,
- A Laner4,
- K Gempel1,
- H Prokisch5,
- H Lochmüller2,
- T Klopstock3,
- M Jaksch1
- 1Metabolic Disease Centre Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics, Academic Hospital Schwabing, Munich, Germany
- 2Friedrich-Baur-Institute and Department of Neurology, Ludwig-Maximilians University, Munich
- 3Department of Neurology, Ludwig-Maximilians University
- 4Medical Genetic Centre, Munich
- 5GSF National Research Centre, Institute of Human Genetics, Munich
- Correspondence to: Dr Rita Horváth Metabolic Disease Centre Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics; Academic Hospital Schwabing, Kölner Platz 1, 80804 Munich, Germany; Rita.Horvath{at}lrz.uni-muenchen.de
Abstract
Detailed clinical, neuroradiological, histological, biochemical, and genetic investigations were undertaken in a child suffering from Leigh syndrome. The clinical symptoms started at age five months and led to a severe progressive neurodegenerative disorder causing epilepsy, psychomotor retardation, and tetraspasticity. Biochemical measurement of skeletal muscle showed a severe decrease in mitochondrial complex II. Sequencing of SDHA revealed compound heterozygosity for a nonsense mutation in exon 4 (W119X) and a missense mutation in exon 3 (A83V), both absent in normal controls. In six additional patients—five with Leigh or Leigh-like syndrome and one with neuropathy and ataxia associated with isolated deficiency of complex II—mutations in SDHA were not detected, indicating genetic heterogeneity.
- DHPLC, denaturing high performance liquid chromatography
- RC, respiratory chain
- SDH, succinate dehydrogenase
- Leigh syndrome
- SDHA
- complex II
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