title: Association and Mutation Analyses of the IRF6 Gene in Families With Nonsyndromic and Syndromic Cleft Lip and/or Cleft Palate.
abstract: OBJECTIVE
  (1) To detect interferon regulatory factor 6 gene (IRF6) mutations in newly recruited Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) families. (2) To test for association, in nonsyndromic cleft lip and/or cleft palate (NSCL/P) and in VWS/PPS families, the single nucleotide polymorphism (SNP) rs642961, from the IRF6 enhancer AP-2α region, alone or as haplotype with rs2235371, a coding SNP (Val274Ile).
  
  
  METHODS
  IRF6 mutation screening was performed by direct sequencing and genotyping of rs642961 and rs2235371 by TaqMan technology.
  
  
  METHODS
  Seventy-one Swedish NSCL/P families, 24 Finnish cleft palate (CP) families, and 24 VWS/PPS families (seven newly recruited) were studied.
  
  
  RESULTS
  Allelic and genotypic frequencies in each phenotype were compared to those of the controls, and no significant difference could be observed. IRF6 gene mutation was detected in six of the seven new VWS/PPS families. Association analysis of the entire VWS/PPS sample set revealed the A allele from rs642961 to be a risk allele. Significant association was detected in the Swedish CP subset of our NSCL/P collection where the G-C haplotype for rs642961-rs2235371 were at risk (P = .013).
  
  
  CONCLUSIONS
  Our results do not support the previously reported association between the A allele of rs642961 and the NSCL phenotype. However, in the VWS/PPS families, the A allele was a risk allele and was, in a large majority (>80%), transmitted on the same chromosome as the IRF6 mutation.
authors: M
authors: M
authors: Pegelow
authors: H
authors: H
authors: Koillinen
authors: M
authors: M
authors: Magnusson
authors: I
authors: I
authors: Fransson
authors: P
authors: P
authors: Unneberg
authors: J
authors: J
authors: Kere
authors: A
authors: A
authors: Karsten
authors: M
authors: M
authors: Peyrard-Janvid
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000483:Alleles; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003560:Cysts / Q000235:genetics*; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005385:Fingers / Q000002:abnormalities*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D007719:Knee Joint / Q000002:abnormalities*; D008046:Lip / Q000002:abnormalities*; D038061:Lower Extremity Deformities, Congenital / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013548:Sweden; D013576:Syndactyly / Q000235:genetics*; D014564:Urogenital Abnormalities / Q000235:genetics*
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors