Co-segregation of MEN2 and Hirschsprung's disease: The same mutation of RET with both gain and loss-of-function?

Masahide Takahashi, Toshihide Iwashita, Massimo Santoro, Stanislas Lyonnet, Gilbert M. Lenoir, Marc Billaud

研究成果: ジャーナルへの寄稿学術論文査読

78 被引用数 (Scopus)


Multiple endocrine neoplasia type 2 (MEN2) and Hirschsprung's disease (HSCR) are two dominantly inherited neurocristopathies ascribed to mutations in the RET gene [Chakravarti, 1996; Pasini et al., 1996; Eng and Mulligan, 1997]. MEN2 is a cancer syndrome comprising three related clinical subtypes: (1) MEN type 2A (MEN2A; MIM 171400) characterized by the association of medullary thyroid carcinoma (MTC), pheochromocytoma (Pheo), and hyperparathyroidism; (2) MEN type 2B (MEN2B; MIM 162300), which includes MTC, Pheo, mucosal neuromas, ganglioneuromatosis of the digestive tract, and skeletal abnormalities; and (3) familial MTC (FMTC; MIM 155240), defined by the sole occurrence of MTC. HSCR (MIM 142623) is a congenital malformation caused by the absence of enteric plexuses in the hindgut, leading to bowel obstruction in neonates. The RET gene (MIM 164761) codes for a transmembrane tyrosine kinase, a component of a multimeric complex that also comprises one of four members of a novel family of glycosylphosphatidylinositol (GPI)- anchored receptor, GFRα(1-4) (e.g., GFRA1, MIM 601496; references are detailed in Baloh et al. [1998]. Four structurally related soluble factors - glial cell line-derived neurotrophic factor (GDNF), neurturin, persephin, and artemin - are the ligands of these multimolecular receptors in which the nature of the GFRα determines the ligand specificity of the complex [see Baloh et al., 1998, for references]. It is well documented that RET/GFRα- 1/GDNF delivers a signal critical for the survival of the early neural crest- derived precursors that colonize the intestine below the rostral foregut and give rise to the enteric nervous plexuses [Gershon, 1997; Cacalano et al., 1998; Enomoto et al., 1998].

ジャーナルHuman Mutation
出版ステータス出版済み - 01-01-1999

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)


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