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Science 22 September 2006:
Vol. 313. no. 5794, p. 1751
DOI: 10.1126/science.1128406
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SUMO1 Haploinsufficiency Leads to Cleft Lip and Palate

Fowzan S. Alkuraya,1* Irfan Saadi,1* Jennifer J. Lund,1 Annick Turbe-Doan,1 Cynthia C. Morton,2 Richard L. Maas1{dagger}

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.

1 Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, NRB-458, 77 Louis Pasteur, Boston, MA 02115, USA.
2 Department 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.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: maas{at}genetics.med.harvard.edu

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