Investigation of SUMO Pathway Genes in the Etiology of Nonsyndromic Cleft Lip with or without Cleft Palate

BACKGROUND: SUMO1 has been implicated as having a role in the causation of cleft lip with or without cleft palate (CLP), both directly and through association studies in humans and, perhaps more controversially, in transgenic mouse studies. METHODS: To screen for sequence variants that might be responsible for human CLP, we performed direct DNA sequence analysis in a well-characterized white European cohort of 192 patients. We screened the genes encoding SUMO1, SUMO2, and SUMO3, as well as the E3 ligases PIAS1 and PIAS2, which are required for sumoylation. Variants were analyzed in a cohort of 192 unaffected white European controls. RESULTS: Only two missense variants were identified, both within SUMO3, however, these were both present in multiple affected individuals and a similar number of controls. Other variants identified, apart from a single synonymous change in PIAS1, were all present within flanking intronic regions distant from splice consensus sites. Moreover, most other variants were previously reported in dbSNP and were shown to be present at a similar frequency in cases and controls. CONCLUSIONS: Our findings indicate that mutations identified in the SUMO-related genes tested, including three novel coding SNPs, do not directly contribute to the incidence of CLP. Birth Defects Research (Part A) 94:459-463, 2012. (C) 2012 Wiley Periodicals, Inc.