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Phenotypic dichotomy in mitochondrial complex II genetic disorders.
B E Baysal1, W S Rubinstein, P E Taschner
1Department of Psychiatry, University of Pittsburgh Medical Center, 3811 O'Hara Street R1445, Pittsburgh, PA 15213, USA. baysalbe@msx.upmc.edu
Journal of Molecular Medicine (Berlin, Germany)
|November 3, 2001
Summary
Mitochondrial complex II gene defects cause distinct disorders. Mutations in SDHA lead to mitochondrial diseases, while SDHB, SDHC, and SDHD mutations cause hereditary paraganglioma, a type of tumor.
Area of Science:
- Biochemistry
- Genetics
- Oncology
Background:
- Mitochondrial complex II (succinate:ubiquinone oxidoreductase) is crucial for the Krebs cycle and electron transport chain.
- Defects in mitochondrial respiratory chain genes can cause severe multi-system disorders.
- Complex II is composed of four nuclear-encoded subunits: SDHA, SDHB, SDHC, and SDHD.
Purpose of the Study:
- To review the genetic and phenotypic spectrum of mitochondrial complex II gene defects.
- To elucidate the dichotomy in disease presentation based on affected subunits.
- To explore the link between complex II mutations and tumorigenesis.
Main Methods:
- Review of current literature on mitochondrial complex II gene defects.
- Analysis of genotype-phenotype correlations.
- Examination of inheritance patterns and genomic imprinting.
Main Results:
- Mutations in SDHA are associated with phenotypes similar to other mitochondrial and Krebs cycle defects.
- Mutations in SDHB, SDHC, and SDHD are linked to hereditary paraganglioma, including pheochromocytomas.
- SDHD mutations exhibit paternal transmission exclusively, indicating genomic imprinting.
Conclusions:
- Mitochondrial complex II gene defects present a phenotypic dichotomy, affecting either mitochondrial function or causing tumors.
- The association of complex II defects with paraganglioma expands the known spectrum of mitochondrial diseases.
- Genomic imprinting is identified as a novel transmission mode in mitochondrial genetics, particularly with SDHD mutations.