Founder SDHB Exon 1 Deletion in Brazilian Patients with Paraganglioma: Further Evidence for An Iberian Founder Effect

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.