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. 2005 Nov 16:6:39.
doi: 10.1186/1471-2350-6-39.

The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency

Jean-Pierre Bayley  1 , Peter Devilee, Peter E M Taschner
Affiliations

The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency

Jean-Pierre Bayley et al. BMC Med Genet. .

Abstract

Background: The SDHA, SDHB, SDHC and SDHD genes encode the subunits of succinate dehydrogenase (succinate: ubiquinone oxidoreductase), a component of both the Krebs cycle and the mitochondrial respiratory chain. SDHA, a flavoprotein and SDHB, an iron-sulfur protein together constitute the catalytic domain, while SDHC and SDHD encode membrane anchors that allow the complex to participate in the respiratory chain as complex II. Germline mutations of SDHD and SDHB are a major cause of the hereditary forms of the tumors paraganglioma and pheochromocytoma. The largest subunit, SDHA, is mutated in patients with Leigh syndrome and late-onset optic atrophy, but has not as yet been identified as a factor in hereditary cancer.

Description: The SDH mutation database is based on the recently described Leiden Open (source) Variation Database (LOVD) system. The variants currently described in the database were extracted from the published literature and in some cases annotated to conform to current mutation nomenclature. Researchers can also directly submit new sequence variants online. Since the identification of SDHD, SDHC, and SDHB as classic tumor suppressor genes in 2000 and 2001, studies from research groups around the world have identified a total of 120 variants. Here we introduce all reported paraganglioma and pheochromocytoma related sequence variations in these genes, in addition to all reported mutations of SDHA. The database is now accessible online.

Conclusion: The SDH mutation database offers a valuable tool and resource for clinicians involved in the treatment of patients with paraganglioma-pheochromocytoma, clinical geneticists needing an overview of current knowledge, and geneticists and other researchers needing a solid foundation for further exploration of both these tumor syndromes and SDHA-related phenotypes.

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Figures

Figure 1
Figure 1
The introductory page of the SDHD mutation database. In addition to summary tables, various search options are also available.
Figure 2
Figure 2
A partial overview of the SDHD table of allelic variants.
Figure 3
Figure 3
The distribution of mutations affecting the coding region (corrected for length of the exon) for SDHB (n = 43) is significantly different from an expected even distribution (ChiSq, p = 0.002) and B) for SDHD (n = 40), mutations occur approximately equally in all four exons (p = 0.99).
Figure 4
Figure 4
The relative occurrence of SDHB vs. SDHD mutations in patients with HN PGL only or pheochromocytoma/extra-adrenal paraganglioma with or without HN PGL.
See this image and copyright information in PMC

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