title: Genomic structure of the gene for the SH2 and pleckstrin homology domain-containing protein GRB10 and evaluation of its role in Hirschsprung disease.
abstract: Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most frequent cause of congenital bowel obstruction. Germline mutations in the RET receptor tyrosine kinase have been shown to cause HSCR. Mice that carry null alleles for RET or for its ligand, glial cell line-derived neurotrophic factor (GDNF), both exhibit complete intestinal aganglionosis and renal defects. Recently, the Src homology 2 (SH2) domain-containing protein Grb10 has been shown to interact with RET in vitro and in vivo, early in development. We have confirmed the map location of GRB10 on human chromosome 7, isolated human BACs containing the gene, elucidated its genomic structure, isolated a highly polymorphic microsatellite marker adjacent to exon 14 and scanned the gene for mutations in a large panel of HSCR patients. No evidence of linkage was detected in HSCR kindreds and no mutations were found in patients. These data suggest that while GRB10 may be important for signal transduction in developing embryos, it does not play an obvious role in HSCR.
authors.affiliation: Department of Genetics, Case Western Reserve University and University Hospitals of Cleveland, Ohio 44106-4955, USA.
authors.forename: M
authors.initials: M
authors.lastname: Angrist
authors.forename: S
authors.initials: S
authors.lastname: Bolk
authors.forename: K
authors.initials: K
authors.lastname: Bentley
authors.forename: S
authors.initials: S
authors.lastname: Nallasamy
authors.forename: M K
authors.initials: MK
authors.lastname: Halushka
authors.forename: A
authors.initials: A
authors.lastname: Chakravarti
mesh_terms: D001798:Blood Proteins; D051383:GRB10 Adaptor Protein; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D010750:Phosphoproteins; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D018909:src Homology Domains
chemical_list: D001798:Blood Proteins; D010750:Phosphoproteins; D011506:Proteins; C039077:platelet protein P47; D051383:GRB10 Adaptor Protein