SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma
| Autor: | Karin van der Tuin, Eleonora P M Corssmit, Birke Bausch, Erik F. Hensen, Jeroen C. Jansen, Hartmut P. H. Neumann, Peter Devilee, Jean-Pierre Bayley |
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| Přispěvatelé: | VU University medical center |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Bayley, J P, Bausch, B, Jansen, J C, Hensen, E F, van der Tuin, K, Corssmit, E P, Devilee, P & Neumann, H P 2023, ' SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma ', Journal of Medical Genetics, vol. 60, no. 1, pp. 25-32 . https://doi.org/10.1136/jmedgenet-2020-107656 Journal of Medical Genetics, 60(1), 25-32. BMJ Publishing Group Journal of Medical Genetics. BMJ PUBLISHING GROUP Journal of Medical Genetics |
| ISSN: | 0022-2593 |
| DOI: | 10.1136/jmedgenet-2020-107656 |
| Popis: | BackgroundTraditional genotype-phenotype correlations for the succinate dehydrogenase-complex II (SDH) genes linkSDHBvariants to thoracic-abdominal pheochromocytoma-paraganglioma (PPGL) andSDHDvariants to head and neck paraganglioma (HNPGL). However, in a recent study we found strong and specific genotype-phenotype associations forSDHDvariants. In the present study we zoom in on the genotype-phenotype associations ofSDHBgene variants, considering the impact of individual gene variants on disease risk and risk of malignancy.MethodsWe analysed two large independent data sets, including a total of 448 patients with PPGL and HNPGL, and studied the association of missense or truncatingSDHBvariants with tumour incidence, age of onset and malignancy risk using binomial testing and Kaplan-Meier analysis.ResultsCompared with missense variants, truncatingSDHBvariants were significantly and consistently more common in patients with PPGL, by a 20 percentage point margin. Malignancy was also significantly more common in truncating versus missense variant carriers. No overall differences in age of PPGL onset were noted between carriers of the two variant types, although some individual variants may differ in certain cases. Missense variants were marginally over-represented among patients with HNPGL, but the difference was not statistically significant.ConclusionSDHBtruncating variants convey an elevated risk for development of both PPGL and malignancy compared with missense variants. These results further support earlier robust associations between truncating variants and PPGL, and also suggest that the two variant types differ in their impact on complex II function, with PPGL/HNPGL tissues displaying differing sensitivities to changes in complex II function. |
| Databáze: | OpenAIRE |
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