Founder SDHB Exon 1 Deletion in Brazilian Patients with Paraganglioma: Further Evidence for An Iberian Founder Effect
TL;DR
Three apparently unrelated Brazilian patients with paragangliomas carrying the same heterozygous germline SDHB exon 1 deletion are reported, reinforcing the high prevalence of this deletion in Brazil and its relevance for targeted genetic testing, family screening, and long-term surveillance strategies.
Abstract
Pheochromocytomas and paragangliomas (PPGLs) are highly heritable neuroendocrine tumors frequently associated with germline pathogenic variants in SDHB. Although large SDHB deletions are rare worldwide, a recurrent 15,678 bp deletion encompassing the promoter region and exon 1 has been described in the Iberian Peninsula and Latin America, suggesting a founder effect. We report three apparently unrelated Brazilian patients with paragangliomas carrying the same heterozygous germline SDHB exon 1 deletion (NM_003000.3: c.1-10413_73-3866del; g.17043962_17059585del). Clinical presentation was heterogeneous, including early-onset secretory paragangliomas and one patient with the 3P association (pheochromocytoma, paraganglioma, and pituitary adenoma). All tumors were surgically treated, and long-term follow-up showed favorable outcomes without metastatic disease. Breakpoint and haplotype analyses confirmed identity with the previously reported Iberian founder variant, supporting a shared ancestral origin. These findings reinforce the high prevalence of this deletion in Brazil and its relevance for targeted genetic testing, family screening, and long-term surveillance strategies.