title: CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate.
abstract: OBJECTIVE
  To assess the association between nonsyndromic (NS) cleft lip with or without cleft palate (CL(P)) and single-nucleotide polymorphisms (SNPs) within the CRISPLD2 gene (cysteine-rich secretory protein LCCL domain containing 2).
  
  
  METHODS
  Four SNPs within the CRISPLD2 gene domain (rs1546124, rs8061351, rs2326398, rs4783099) were genotyped to test for association via family-based association methods.
  
  
  METHODS
  A total of 5826 individuals from 1331 families in which one or more family member is affected with CL(P).
  
  
  RESULTS
  Evidence of association was seen for SNP rs1546124 in U.S. (p  =  .02) and Brazilian (p  =  .04) Caucasian cohorts. We also found association of SNP rs1546124 with cleft palate alone (CP) in South Americans (Guatemala and ECLAMC) and combined Hispanics (Guatemala, ECLAMC, and Texas Hispanics; p  =  .03 for both comparisons) and with both cleft lip with cleft palate (CLP; p  =  .04) and CL(P) (p  =  .02) in North Americans. Strong evidence of association was found for SNP rs2326398 with CP in Asian populations (p  =  .003) and with CL(P) in Hispanics (p  =  .03) and also with bilateral CL(P) in Brazilians (p  =  .004). In Brazilians, SNP rs8061351 showed association with cleft subgroups incomplete CL(P) (p  =  .004) and unilateral incomplete CL(P) (p  =  .003). Prediction of SNP functionality revealed that the C allele in the C471T silent mutation (overrepresented in cases with CL(P) presents two putative exonic splicing enhancer motifs and creates a binding site AP-2 alpha, a transcription factor involved in craniofacial development.
  
  
  CONCLUSIONS
  Our results support the hypothesis that variants in the CRISPLD2 gene may be involved in the etiology of NS CL(P).
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.forename: Renato
authors.initials: R
authors.lastname: Menezes
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Renata F
authors.initials: RF
authors.lastname: Fonseca
authors.forename: Stephen
authors.initials: S
authors.lastname: Tropp
authors.forename: Manika
authors.initials: M
authors.lastname: Govil
authors.forename: Jose M
authors.initials: JM
authors.lastname: Granjeiro
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Imoehl
authors.forename: M Adela
authors.initials: MA
authors.lastname: Mansilla
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castilla
authors.forename: Iêda M
authors.initials: IM
authors.lastname: Orioli
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Czeizel
authors.forename: Lian
authors.initials: L
authors.lastname: Ma
authors.forename: Brett T
authors.initials: BT
authors.lastname: Chiquet
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
mesh_terms: D000225:Adenine; D017398:Alternative Splicing / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D015331:Cohort Studies; D003596:Cytosine; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006147:Guanine; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000235:genetics; D013941:Thymine; D050656:Transcription Factor AP-2 / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C525599:CRISPLD2 protein, human; D015815:Cell Adhesion Molecules; D050835:Interferon Regulatory Factors; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D006147:Guanine; D003596:Cytosine; D000225:Adenine; D013941:Thymine
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