title: [Mutations of RET proto-oncogene in Hirschsprung disease].
abstract: Hirschsprung's disease (HSCR) is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates and megacolon in infants and adults. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR. Recently, a gene for HSCR has been mapped to chromosome 10q11.2. No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest. Here we report on nonsense and missense mutations in the extracellular domain of the RET protein (exons 2, 3, 5 and 6) in 6 unrelated probands and show that the mutant genotypes segregate with the disease in HSCR families. Mutations of RET have been previously reported in multiple endocrine neoplasia type 2A (MEN 2A). Thus, germ-line mutations of the RET gene may contribute either to developmental anomalies in HSCR or to inherited predisposition to cancer in MEN 2A.
authors.affiliation: Service de Génétique Médicale, INSERM U. 393, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: P
authors.initials: P
authors.lastname: Edery
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: A
authors.initials: A
authors.lastname: Pelet
authors.forename: E
authors.initials: E
authors.lastname: Dow
authors.forename: L
authors.initials: L
authors.lastname: Abel
authors.forename: S
authors.initials: S
authors.lastname: Holder
authors.forename: C
authors.initials: C
authors.lastname: Nihoul-Fékéte
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: A
authors.initials: A
authors.lastname: Munnich
mesh_terms: D018389:Codon, Nonsense; D029721:Drosophila Proteins; D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila
vernacular_title: Des mutations du proto-oncogène RET dans la maladie de Hirschsprung.