SUMO1 Haploinsufficiency Leads to Cleft Lip and Palate

American Association for the Advancement of Science (AAAS) - Tập 313 Số 5794 - Trang 1751-1751 - 2006
Fowzan S. Alkuraya1,2, Irfan Saadi1,2, Jennifer J. Lund1,2, Annick Turbé-Doan1,2, Cynthia C. Morton1, Richard L. Maas1,2
1Department of Obstetrics and Gynecology and Reproductive Biology and Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, NRB-160d, 77 Louis Pasteur, Boston, MA 02115, USA.
2Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, NRB-458, 77 Louis Pasteur, Boston, MA 02115, USA.

Tóm tắt

The posttranslational modification sumoylation can have multiple effects on its substrate proteins. We studied a patient with isolated cleft lip and palate and a balanced chromosomal translocation that disrupts the SUMO1 (small ubiquitin-related modifier) gene, resulting in haploinsufficiency. In mouse, we found that Sumo1 is expressed in the developing lip and palate and that a Sumo1 hypomorphic allele manifests an incompletely penetrant orofacial clefting phenotype. Products of several genes implicated in clefting are sumoylated, and the Sumo1 hypomorphic allele interacts genetically with a loss-of-function allele for one of these loci. Thus, sumoylation defines a network of genes important for palatogenesis.

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We thank G. Gill for generously providing expression vectors and members of the Developmental Genome Anatomy Project Consortium for their support. We also thank the patient her family and B. J. Negrini for their help and Unique for their assistance in recruitment. This work was supported by NIH grants GM061365 (C.C.M.) DE11697 and DE015246 (R.L.M.) and HD043430 to D. Beier (A.T.-D.) and a Canadian Institutes of Health Research postdoctoral fellowship (I.S.).

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American Association for the Advancement of Science (AAAS)

Tập 313 Số 5794

1751-1751

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