Further evidence suggesting a role for variation in ARHGAP29 variants in nonsyndromic cleft lip/palate

Ariadne Letra, Lorena Maili, John B. Mulliken, Edward Buchanan, Susan H Blanton, Jacqueline T. Hecht

Research output: Contribution to journalArticle

9 Scopus citations


Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect of complex etiology. Several genes have been implicated in the etiology of NSCL/P, although only a few have been replicated across datasets. Methods: ARHGAP29 was suggested as a candidate gene for NSCL/P as it is located in close proximity to ABCA4 (1p22), a gene previously identified in a genome-wide association study of NSCL/P. Results: Rare, potentially damaging, coding variants in ARHGAP29 were found in NSCL/P cases, and its expression was detected during murine craniofacial development. In this study, we investigated whether variations in ARHGAP29 were associated with NSCL/P in our family based dataset. Five single-nucleotide polymorphisms (SNPs) flanking and within ARHGAP29 were genotyped in our NSCL/P datasets consisting of simplex and multiplex families of non-Hispanic white (NHW, primarily European) and Hispanic ethnicities. Results showed strong association of three ARHGAP29 SNPs with NSCL/P in the NHW families. Two intronic SNPs (rs1541098 and rs3789688) showed strong association with NSCL/P in all NHW families (p=0.0005 and p=0.0002, respectively), and simplex NHW families (p=0.003 for both SNPs). A SNP in the 3′ untranslated region (rs1576593) also showed strong association with NSCL/P in all NHW families (p=0.002), and the multiplex subset (p=0.002). ARHGAP29 SNP haplotypes were also associated with NSCL/P. Evidence of gene-gene interaction was found between ARHGAP29 and additional cleft susceptibility genes. Conclusion: This study further supports ARHGAP29 as a candidate gene for human NSCL/P in families of Caucasian descent.

Original languageEnglish (US)
Pages (from-to)679-685
Number of pages7
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Issue number9
StatePublished - 2014



  • ARHGAP29
  • Association
  • Cleft lip/palate
  • Gene
  • Gene interaction
  • Haplotype

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Embryology

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