title: Heterogeneity and low detection rate of RET mutations in Hirschsprung disease.
abstract: Mutations in some exons of the RET proto-oncogene were recently observed in Hirschsprung patients. Using DNA polymorphisms and single-strand conformation polymorphism analysis for the whole coding sequence of the RET proto-oncogene, 82 unrelated Hirschsprung patients were screened systematically. A total of 4 complete deletions of RET and 12 point mutations were identified, each present in no more than one patient and distributed along the whole gene. De novo mutations could be documented in 4 patients. Southern blot and fluorescence in situ hybridization analysis carried out in a restricted number of patients did not reveal any deletion of RET. The low efficiency in detecting mutations of RET in Hirschsprung patients (20%) may originate mainly from genetic heterogeneity.
authors.affiliation: Laboratorio di Genetica Molecolare, Istituto G. Gaslini, Genova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Yin
authors.forename: V
authors.initials: V
authors.lastname: Barone
authors.forename: M
authors.initials: M
authors.lastname: Seri
authors.forename: A
authors.initials: A
authors.lastname: Bolino
authors.forename: R
authors.initials: R
authors.lastname: Bocciardi
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.forename: B
authors.initials: B
authors.lastname: Pasini
authors.forename: T
authors.initials: T
authors.lastname: Tocco
authors.forename: M
authors.initials: M
authors.lastname: Lerone
authors.forename: S
authors.initials: S
authors.lastname: Cywes
mesh_terms: D015139:Blotting, Southern; D029721:Drosophila Proteins; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; 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; 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