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


Hirschsprung disease (HSCR) is sometimes associated with a set of characteristics including mental retardation, microcephaly, and distinct facial features1,2,3, but the gene mutated in this condition has not yet been identified. Here we report that mutations in SIP1, encoding Smad interacting protein-1, cause disease in a series of cases. SIP1 is located in the deleted segment 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 crest development.

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Figure 1: Physical and cytogenetic examinations.
Figure 2: Physical map of the 5-Mb chromosome 2q22 translocation breakpoint of patient 1 and the position of SIP1.

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We thank the families and patients for participation; S. Tsuji for critical reading of this manuscript and discussions; and K. Miura and S. Miyazaki for help with clinical studies. This work was supported by grants from Ministry of Education, Science, Sports and Culture of Japan (to N.W. and K.K.) and Tsubaki Memorial Neuroscience Research Foundation (to N.W.).

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Correspondence to Nobuaki Wakamatsu.

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Wakamatsu, N., Yamada, Y., Yamada, K. et al. Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease. Nat Genet 27, 369–370 (2001).

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