Abstract

Background: Hereditary susceptibility to familial paraganglioma syndromes is mainly due to mutations in one of six genes, including three of the four genes encoding the subunits of the mitochondrial succinate dehydrogenase complex II. Alhough prevalence, penetrance and clinical characteristics of patients carrying point mutations affecting the genes encoding succinate dehydrogenase have been well studied, little is known regarding these clinical features in patients with gross deletions. Recently, we found two unrelated Spanish families carrying the previously reported SDHB exon 1 deletion, and suggested that this chromosomal region could be a hotspot deletion area. Methods: Here, we present the molecular characterization of this apparently prevalent mutation in three new families, and discuss whether this recurrent mutation is due either to the presence of a founder effect or to a hotspot. Results: The breakpoint analysis showed that all Peninsular families described harbour the same exon 1 deletion, and that a different breakpoint-junction segregates in an affected French pedigree. Conclusions: After haplotyping the SDHB region, we concluded that the deletion detected in Peninsular people is probably due to a founder effect. Regarding the clinical characteristics of patients with this alteration, it seems that the presence of gross deletions rather than point mutations is more likely related to abdominal presentations and younger age of onset. Moreover, we found for the first time a patient with neuroblastoma and a germline SDHB deletion, but it seems that this pediatric neoplasia in a pheochromocytoma family is not a key component of this disease.