title: Investigation of SUMO pathway genes in the etiology of nonsyndromic cleft lip with or without cleft palate.
abstract: 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.
authors.affiliation: UCL Institute of Child Health, London, United Kingdom.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Carta
authors.forename: Erwin
authors.initials: E
authors.lastname: Pauws
authors.forename: Anna C
authors.initials: AC
authors.lastname: Thomas
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mengrelis
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Moore
authors.forename: Melissa
authors.initials: M
authors.lastname: Lees
authors.forename: Philip
authors.initials: P
authors.lastname: Stanier
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics; D025842:SUMO-1 Protein / Q000235:genetics; D017422:Sequence Analysis, DNA; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics; D014452:Ubiquitins / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C106529:PIAS1 protein, human; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins