Síndrome de paraganglioma familiar: expresividad clínica y relevancia de una nueva mutación en SDHB

Abstract

Background and objectiveAdvances in molecular biology have discovered new genes involved in the development of familial paraganglioma syndrome (PGL) including those encoding mitochondrial succinate dehydrogenase complex (SDH). We describe the diagnosis, clinical expression and genetic counselling in a family diagnosed of PGL due to a new SDHB mutation. Patients and methodGenetic study by PCR-direct sequencing SDHB gene and biochemical determination in blood/urine fractionated catecholamine 24h, metanephrines and conventional (computed tomography/magnetic resonance imaging) and functional imaging (123I-MIBG) in all members of a family diagnosed of PGL. ResultDNA sequencing showed a non-described SDHB heterozygous mutation (c.287-3C>G intron3/exon4) in 5 of the subjects (71%). The estimated penetrance of the mutation's carriers was 40%, with a mean age of 35 years at diagnosis. All patients with active illness required surgical treatment after imaging and laboratory confirmation. ConclusionsWe describe the pathogenicity, diagnostic algorithm, genetic counselling and clinical expression of a new SDHB mutation (c.287-3C>G) in a family diagnosed of PGL.