Novel Causative Mutation in a Japanese Family with Hirschsprung's Disease: Case Report and Factors Impacting Disease Severity.

gene variances confer susceptibility to Hirschsprung's disease (HSCR) with pathogenetic mutations being identified in half of familial cases. This investigation of familial HSCR was aimed to clarify the relationship between genetic mutations and clinical phenotype using next-generation sequencing. A novel c2313C > G(D771E) mutation was identified in all three affected family members. The mutation involved the kinase domain, which is believe to impair activity and intestinal function. A second mutation, c1465G > A(D489N), was found only in the extensive aganglionosis case. We conclude that the novel c2313C > A(D771E) mutation in may be pathogenic for HSCR, while the c1465C > G(D489N) mutation may be related to phenotype severity.