Impact factor'2009=1.324


Journal of Applied Genetics 47(3), 2006, pp. 261-267

Single nucleotide polymorphisms in the RET gene and their correlations with Hirschsprung disease phenotype

Robert Smigiel, Arleta Lebioda, Dariusz Patkowski, Jerzy Czernik, Tadeusz Dobosz, Karolina Pesz, Monika Kaczmarz, Maria M. Sasiadek

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.

Key words: genotype-phenotype correlation, Hirschsprung disease, polymorphisms, RET gene.

Correspondence: R. Smigiel, Genetics Department, Marcinkowskiego 1, 50-368 Wroclaw, Poland; e-mail:

Full text article: