title: Investigation of germline GFR alpha-1 mutations in Hirschsprung disease.
abstract: Inactivating mutations of the RET proto-oncogene and of one of its soluble ligand molecules, glial cell line derived neurotrophic factor (GDNF), have been found in a subset of patients with Hirschsprung disease (HSCR). However, the majority of HSCR mutations remain unidentified. As normal RET function requires a multicomponent ligand complex for activation, other members of the RET ligand complex are primary candidates for these mutations. We investigated the presence of mutations in another member of the RET signalling complex, GDNF family receptor alpha-1 (GFR alpha-1), in a panel of 269 independent cases of HSCR. We identified 10 polymorphisms at the GFR alpha-1 locus. Surprisingly, however, we did not identify any sequence variants in our HSCR population that were not also present in a normal control population. Our data suggest that mutations of the GFR alpha-1 gene are not a common aetiological event in HSCR.
authors: Department of Pathology, Queen's University, Kingston, Ontario, Canada.
authors: S M
authors: SM
authors: Myers
authors: R
authors: R
authors: Salomon
authors: A
authors: A
authors: Goessling
authors: A
authors: A
authors: Pelet
authors: C
authors: C
authors: Eng
authors: A
authors: A
authors: von Deimling
authors: S
authors: S
authors: Lyonnet
authors: L M
authors: LM
authors: Mulligan
mesh_terms: D017398:Alternative Splicing; D029721:Drosophila Proteins; D005091:Exons; D014644:Genetic Variation; D018095:Germ-Line Mutation; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; 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: D029721:Drosophila Proteins; C494987:GFRA1 protein, human; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; 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