title: Penetrance and clinical consequences of  a gross SDHB deletion in a large family.
abstract: Mutations in the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) are inherited in an autosomal dominant manner and are associated with hereditary paraganglioma (PGL) and pheochromocytoma. The phenotype of patients with SDHB point mutations has been previously described. However, the phenotype and penetrance of gross SDHB deletions have not been well characterized as they are rarely described. The objective was to describe the phenotype and estimate the penetrance of an exon 1 large SDHB deletion in one kindred. A retrospective and prospective study of 41 relatives across five generations was carried out. The main outcome measures were genetic testing, clinical presentations, plasma catecholamines and their O-methylated metabolites. Of the 41 mutation carriers identified, 11 were diagnosed with PGL, 12 were found to be healthy carriers after evaluation, and 18 were reportedly healthy based on family history accounts. The penetrance of PGL related to the exon 1 large SDHB deletion in this family was estimated to be 35% by age 40. Variable expressivity of the phenotype associated with a large exon 1 SDHB deletion was observed, including low penetrance, diverse primary PGL tumor locations, and malignant potential.
authors.affiliation: Reproductive and Adult Endocrinology Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1109, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Solis
authors.forename: N
authors.initials: N
authors.lastname: Burnichon
authors.forename: H J L M
authors.initials: HJ
authors.lastname: Timmers
authors.forename: M J
authors.initials: MJ
authors.lastname: Raygada
authors.forename: A
authors.initials: A
authors.lastname: Kozupa
authors.forename: M J
authors.initials: MJ
authors.lastname: Merino
authors.forename: D
authors.initials: D
authors.lastname: Makey
authors.forename: K T
authors.initials: KT
authors.lastname: Adams
authors.forename: A
authors.initials: A
authors.lastname: Venisse
authors.forename: A-P
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: K
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000328:Adult; D005091:Exons; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D021122:Protein Subunits / Q000235:genetics; D017384:Sequence Deletion; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D021122:Protein Subunits; D013385:Succinate Dehydrogenase