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