title: Germline succinate dehydrogenase subunit D mutation segregating with familial non-RET C cell hyperplasia.
abstract: C cell hyperplasia is associated with medullary carcinoma of the thyroid in the inherited MEN2 syndromes, in which the great majority of cases have been shown to be due to a mutation in the RET oncogene. We report a study of a family with C cell hyperplasia and hypercalcitoninemia in which no cases of medullary carcinoma have yet occurred and which lacked an identifiable causative RET mutation. Four of the family members showed hypercalcitoninemia, and marked C cell hyperplasia was present in each of the three in whom thyroidectomy has been performed. We investigated the possible involvement of the SDHD gene, because somatic and germline mutations in this gene have been found in a variety of tumors of neural crest-derived tissue. A germline mutation in exon 2 of the SDHD gene (c149 A-G, His 50 Arg) was found in six members of the family; all the four available members with hypercalcitoninemia possessed the mutation. One of the five available members without hypercalcitoninemia, an 18-yr-old female, also showed the mutation. We conclude that we have identified a new syndrome, characterized by familial non-RET C cell hyperplasia. Our studies suggest that a mutation in SDHD may be causative. These observations have implications for apparently incidental cases of hypercalcitoninemia or C cell hyperplasia.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, Porto 4200-465, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: José
authors.initials: J
authors.lastname: Teixeira-Gomes
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Honavar
authors.forename: Dillwyn
authors.initials: D
authors.lastname: Williams
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
mesh_terms: D000328:Adult; D002116:Calcitonin / Q000097:blood; D004252:DNA Mutational Analysis; D005192:Family Health; D018095:Germ-Line Mutation; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics* / Q000473:pathology; D006965:Hyperplasia; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics*; D010375:Pedigree; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*; D013959:Thyroid Diseases / Q000235:genetics* / Q000473:pathology; D013961:Thyroid Gland / Q000473:pathology
chemical_list: D015513:Oncogene Proteins; D002116:Calcitonin; D013385:Succinate Dehydrogenase; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases