title: Close linkage with the RET protooncogene and boundaries of deletion mutations in autosomal dominant Hirschsprung disease.
abstract: Tight linkage with the RET proto-oncogene (Zmax = 3.41 at theta = 0.00), analysis of recombinants and detection of a familial microdeletion in a large pedigree restrict the mapping of the Hirschsprung (HSCR) gene previously localized on proximal 10q. The molecular characterization of the familial microdeletion and of 3 additional cytogenetically visible de novo deletions, isolated in somatic cell hybrids, identify a smallest region of overlap of 250 Kb. This contains the RET proto-oncogene where missense mutations causing multiple endocrine neoplasia type 2A (MEN 2A) phenotype were recently found. The pentagastrin test (which detects preclinical forms of MEN 2A or B) is negative in adult HSCR patients with deletions of the RET gene. This represents a good candidate for the search of mutations causing HSCR.
authors.affiliation: Laboratory of Molecular Genetics, G.Gaslini Institute, Genova, Quarto, Italy.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.forename: B
authors.initials: B
authors.lastname: Pasini
authors.forename: I
authors.initials: I
authors.lastname: Matera
authors.forename: M P
authors.initials: MP
authors.lastname: Bicocchi
authors.forename: V
authors.initials: V
authors.lastname: Barone
authors.forename: R
authors.initials: R
authors.lastname: Bocciardi
authors.forename: H
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: D
authors.initials: D
authors.lastname: Weber
authors.forename: M
authors.initials: M
authors.lastname: Devoto
mesh_terms: D002460:Cell Line; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D029721:Drosophila Proteins; D005260:Female; D017353:Gene Deletion; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009377:Multiple Endocrine Neoplasia / Q000235:genetics; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D005819:Genetic Markers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila