Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease

Hirschsprung disease (HSCR) is sometimes associated with a set of character istics including mental retardation, microcephaly, and distinct facial feat ures(1-3), but the gene mutated in this condition has not yet been identifi ed. Here we report that mutations in SIP1, encoding Smad interacting protei n-1, cause disease in a series of cases. SIP1 is located in the deleted seg ment at 2q22 from a patient with a de novo t(2;13)(q22;q22) translocation, SIP1 seems to have crucial roles in normal embryonic neural and neural cres t development.