ArticleThe Journal of clinical investigation2026
Functional characterization of SDHB variants: Advancing succinate dehydrogenase biology and variant curation in hereditary paraganglioma.
Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Germline variants in the gene encoding succinate dehydrogenase subunit B (SDHB) occur in around 10% of all patients with pheochromocytomas and paragangliomas (PPGLs). Diagnosis of these variants has profound implications not only for the patient but also their first-degree relatives in terms of risk for PPGLs and other SDHB-associated tumors (renal cell cancer and gastrointestinal stromal tumors). Appropriate surveillance of SDHB variant carriers is associated with reduced mortality from these cancers. Curation of disease-causing (pathogenic) variants from benign variants is therefore crucial; however, this task is often difficult for missense variants when their impact on biological function is unclear. In this issue of the JCI, Lee et al. have described a newly developed cellular complementation assay for SDHB function that may assist variant curation in clinical practice and thereby improve outcomes for patients inheriting these cancer-risk variants.
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