title: A rare extracellular D631Y germline mutation of the RET proto-oncogene in two Korean families with multiple endocrine neoplasia 2A.
abstract: A mutation in codon 631 of exon 11 of the RET proto-oncogene is extremely rare in the patients with multiple endocrine neoplasia type 2A (MEN 2A). We report here on a rare extracellular mutation of the RET gene that led to the substitution of a tyrosine for an aspartate in codon 631 (D631Y, GAC to TAC) in two Korean families with MEN 2A. Eleven individuals from two unrelated families were found to have the D631Y germline mutation. Among them, medullary thyroid carcinoma (MTC) was identified in five patients: four of them had MEN 2A and one had familial MTC. They had tumors 2 cm or less in the greatest dimension that were limited to the thyroid, and they had a relatively old age above 30 at the time of diagnosis. Pheochromocytoma was detected in six patients including the four patients who had MEN 2A. All had adrenal tumors greater than 3 cm in the greatest dimension, and four of them had bilateral tumors. Two of six patients suffering with pheochromocytoma had no clinical evidence of MTC at the time of diagnosis. None had any evidence of hyperparathyroidism. This genetic profile might be related to the less vigorous clinical disease behavior and the late onset of MTC. In addition, pheochromocytoma might be the first manifestation prior to the development of MTC in some patients with the D631Y mutation. This report is the first description of the clinical characteristics of the D631Y germline mutation in the families with MEN 2A.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Bae
authors.forename: Dae-Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Ji Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.forename: Young Duk
authors.initials: YD
authors.lastname: Song
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000328:Adult; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics*; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret