title: C618R mutation in exon 10 of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease.
abstract: The cosegregation of multiple endocrine neoplasia (MEN) type 2A with Hirschsprung's disease (HSCR), two diseases associated with mutation of the RET proto-oncogene, is infrequent. A 30-yr-old man was referred for screening of MEN 2A. Surgery for HSCR was performed at 4 yr of age. Basal and pentagastrin-stimulated calcitonin levels were abnormal. Histological examination of the thyroid confirmed bilateral medullary thyroid carcinoma. Screening of family members revealed six subjects with medullary thyroid carcinoma or abnormal pentagastrin-stimulated calcitonin test; one had an unilateral pheochromocytoma and two were affected with HSCR. DNA sequence analysis showed a heterozygote C618R mutation in exon 10 of the RET proto-oncogene in the proband and his mother, as well as in second-degree relatives with MEN 2A phenotype or HSCR. In this study, we report on a novel kindred with MEN 2A and HSCR phenotype associated with a point mutation (C618R) in one of the cysteine codons at the extracellular domain of the RET proto-oncogene.
authors.affiliation: Service d'Endocrinologie, CHU Rangueil, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Caron
authors.forename: T
authors.initials: T
authors.lastname: Attié
authors.forename: D
authors.initials: D
authors.lastname: David
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: F
authors.initials: F
authors.lastname: Brousset
authors.forename: P
authors.initials: P
authors.lastname: Roger
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
mesh_terms: D000328:Adult; D002116:Calcitonin / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000473:pathology; D029721:Drosophila Proteins; D005091:Exons; D005260:Female; D006627:Hirschsprung Disease / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010418:Pentagastrin; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000473:pathology
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D010418:Pentagastrin