Background: Hirschsprung's disease (HSCR), or aganglionic megacolon, is a hereditable disease of the enteric nervous system. It is an embryonic developmental disorder characterized by the absence of ganglion cells in the lower enteric plexus. Gut motility is compromised in HSCR, with consequent risk of intestinal obstruction.
Methods: We sequenced the RET gene and characterized the clinical manifestations in 15 unrelated Chinese patients (9 males, 6 females; age range, 2-21 years) with sporadic HSCR. Genomic DNA extraction, PCR and DNA sequence analysis were performed according to standard procedures.
Results: We identified heterozygous RET gene mutations in 2 patients. The mutations included a missense mutation in exon 2 (CGC --> CAC) resulting in a substitution of arginine by histidine at codon 67 (patient 1), and a missense mutation in exon 3 (TAC --> AAC) resulting in a substitution of tyrosine by asparagine at codon 146 (patient 2). The pathological findings disclosed short-segment HSCR in patient 1 and long-segment HSCR in patient 2, respectively.
Conclusion: We identified RET gene mutations in 2 of 15 patients with HSCR in Taiwan. The Y146N mutation we identified was novel.