SUMO1 haploinsufficiency leads to cleft lip and palate.
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.
Alkuraya
Fowzan S
FS
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, NRB-458, 77 Louis Pasteur, Boston, MA 02115, USA.
Saadi
Irfan
I
Lund
Jennifer J
JJ
Turbe-Doan
Annick
A
Morton
Cynthia C
CC
Maas
Richard L
RL
D000328:Adult; D000818:Animals; D002460:Cell Line; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007621:Karyotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010159:Palate / Q000196:embryology / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000235:genetics* / Q000502:physiology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism; D014178:Translocation, Genetic
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; C501156:Eya1 protein, mouse; D017027:Protein Tyrosine Phosphatases