Background/purpose: Hirschsprung's disease (HSCR) is a congenital abnormality that can cause an intestinal obstruction. Although HSCR demonstrates a sex-modified polygenic inheritance with contributions from multiple genes, mutations in the RET gene are believed to be the major sign of susceptibility in the development of disease. The allele frequency of polymorphisms was mostly tested in the American and European population, but the data of an ethnically diverse nonwhite population are unclear.
Methods: All 21 exons and intron/exon boundaries of the RET gene in 18 Korean patients with sporadic HSCR and 84 normal individuals were screened using polymerase chain reaction amplification and direct sequencing.
Results: A total of 11 different nucleotide substitutions were identified. Of these, 2 were new missense mutations (C558Y, cysteine-rich domain; R844W, tyrosine kinase domain) and 9 previously described variants. This study also analyzed the haplotypes for the association between the variants identified with HSCR, but the estimated RET haplotypes did not show any disease risk.
Conclusions: This study identified additional mutations of RET gene, which represents the first comprehensive genetic dissection of sporadic HSCR disease in Koreans.