title: Mutational analysis of the RET and GDNF gene in children with hypoganglionosis.
abstract: Germline mutations of the RET (10q11.2) have been reported in Hirschsprung's disease (HSCR) at a rate of 15-45%. Recently, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET, and GDNF (5p12-p13.1) mutations were also found in association with RET mutations in HSCR patients. We analysed the DNA sequence of RET and the GDNF of patients with hypoganglionosis. We investigated the germline mutation in 5 patients histologically diagnosed with hypoganglionosis. DNAs were extracted from peripheral blood lymphocytes of these patients. The PCR primers were designed for RET tyrosine kinase domain (exon 13-17) and GDNF (exon 1-2). The DNA sequence was determined using a direct DyeDeoxy Terminator Cycle method. The analysis of RET showed silent mutation at the codon 769 (CTT-->CTG) by DNA polymorphism in all patients. No other mutation of the RET or GDNF was evident. These results suggest that the RET or GDNF may not contribute to the pathogenesis of hypoganglionosis, which is suspected to be genetically different from HSCR.
authors.affiliation: Division of Surgery, Children's Research Hospital, Kyoto Prefectural University of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Shimotake
authors.forename: H
authors.initials: H
authors.lastname: Tomiyama
authors.forename: N
authors.initials: N
authors.lastname: Iwai
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020794:Receptor Protein-Tyrosine Kinases