Penetrance and clinical consequences of a gross SDHB deletion in a large family

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 descr...

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Bibliographic Details
Published in:Clinical genetics 2009-04, Vol.75 (4), p.354-363
Main Authors: Solis, DC, Burnichon, N, Timmers, HJLM, Raygada, MJ, Kozupa, A, Merino, MJ, Makey, D, Adams, KT, Venisse, A, Gimenez-Roqueplo, A-P, Pacak, K
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Exons
Family Health
Female
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genes
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Genotype & phenotype
Humans
Male
Medical genetics
Medical sciences
Molecular and cellular biology
Mutation
Neurology
paraganglioma
Paraganglioma - genetics
Paraganglioma - pathology
Pedigree
Penetrance
Phenotype
pheochromocytoma
Protein Subunits - genetics
SDHB deletion
Sequence Deletion
Succinate Dehydrogenase - genetics
succinate dehydrogenase subunit B
Tumors
Tumors of the nervous system. Phacomatoses
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Description
Summary: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.
ISSN:0009-9163
1399-0004
DOI:10.1111/j.1399-0004.2009.01157.x