Dutch founder SDHB exon 3 deletion in patients with pheochromocytoma-paraganglioma in South Africa
Objective: Screening studies have established genetic risk profiles for di seases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma–paraganglioma (PPGL). Founder effects play an important role in the regional/n ational epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration. The role of Dutch founder effects in So uth Africa has not been explored in PPGL. Design: We performed a single-center study in South Africa of the ge... Mehr ...
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Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2022 |
Reihe/Periodikum: | Endocrine Connections, Vol 11, Iss 1, Pp 1-8 (2022) |
Verlag/Hrsg.: |
Bioscientifica
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Schlagwörter: | sdhb / founder mutation / paraganglioma / pheochromocytoma / south africa / dutch / netherlands / Diseases of the endocrine glands. Clinical endocrinology / RC648-665 |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-27409702 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://doi.org/10.1530/EC-21-0560 |
Objective: Screening studies have established genetic risk profiles for di seases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma–paraganglioma (PPGL). Founder effects play an important role in the regional/n ational epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration. The role of Dutch founder effects in So uth Africa has not been explored in PPGL. Design: We performed a single-center study in South Africa of the germline genetic causes of isolated/syndromic neuroendocrine tumors. Methods: Next-generation panel, Sanger sequencing and multiplex ligand-dependent probe amplification for endocrine neoplasia risk genes. Results: From a group of 13 patients, we identified 6 with PPGL, 4 with sporadic or familial isolated pituitary adenomas, and 3 with clinical MEN1; genetic variants were identified in 9/13 cases. We identified the Dutch founder exon 3 deletion in SDHB in two apparently unrelated individuals with distinct ethnic backgrounds that had metastatic PPGL. Asymptomatic carriers with this Dutch founder SDHB exon 3 deletion were also identified. Other PPGL patients had variants in SDHB, and SDHD and three MEN1 variants were identified among MEN1 and young-onset pituitary adenoma pat ients. Conclusions: This is the first identification of a Dutch founder effect for PP GL in South Africa. Awareness of the presence of this exon 3 SDHB deletion could promote targeted screening at a local level. Insights into PPGL genetics in South Africa could be achieved by studying existing patient databases for Dutch founder mutations in SDHx genes.