title: Single nucleotide polymorphisms in the RET gene and their correlations with Hirschsprung disease phenotype.
abstract: Hirschsprung disease (HSCR) is a congenital, heterogeneous disorder, characterized by the absence of intestinal ganglion cells. Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR. The aim of this study was to analyse if the HSCR phenotype in the Polish population is associated with the presence of polymorphisms in exons 2, 3, 7, 11, 13, 14 and 15 of the RET gene. Molecular results were compared with clinical and long-term follow-up data in 70 Polish patients with HSCR (84.3% with a short segment and 15.7% with a long segment of aganglionic gut). Single-nucleotide polymorphisms were analysed by using the minisequencing SNaPshot multiplex method. The 135G>A polymorphism in RET exon 2 was overrepresented in HSCR patients, compared with a healthy control group. Moreover, the 135G>A variant was shown to be associated with the severe HSCR phenotype. Two other polymorphisms, 2071G>A in exon 11 and 2712C>G in exon 15, were underrepresented in the patients. The results confirm that these RET polymorphisms play a role in the aetiology of HSCR.
authors.affiliation: Genetics Department, Medical University, Wrocław, Poland. smigiel@gen.am.wroc.pl
authors.forename: Robert
authors.initials: R
authors.lastname: Smigiel
authors.forename: Arleta
authors.initials: A
authors.lastname: Lebioda
authors.forename: Dariusz
authors.initials: D
authors.lastname: Patkowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Czernik
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Dobosz
authors.forename: Karolina
authors.initials: K
authors.lastname: Pesz
authors.forename: Monika
authors.initials: M
authors.lastname: Kaczmarz
authors.forename: Maria M
authors.initials: MM
authors.lastname: Sasiadek
mesh_terms: D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D017931:DNA Primers; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human