Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Non-Syndromic Orofacial Cleft in Saudi Arabian Patients

Heba Jafar Sabbagh (Lead / Corresponding author), Nicola Innes, Sherif Edris Ahmed, Azeez Butali, Eman Abdulbaset Alnamnakani, Sari Rabah, Mustafa A. Hamdan, Nasir Alhamlan, Fatma D. Abdulhameed, Mona Hassan Ahmed Hassan, Hadiah Bassam Al Mahdi, Najlaa M. Alamoudi, Sumer M. Alaki, Peter Mossey

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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Objective: Nonsyndromic orofacial cleft (NSOFC) including cleft lip with or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental etiological factors. In this study we investigated the association between CL±P and CP, and two polymorphisms previously determined using genome-wide association studies, as well as the association between consanguinity and CL±P and CP.

Methods: DNA was extracted from saliva specimens from 171 triads consisting of affected individuals and their parents, as well as 189 control triads (matched for age, gender, and location) that were recruited from 11 referral hospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located in the VAX1 gene were genotyped using real-time polymerase chain reaction. A transmission disequilibrium test was carried out using the Family-Based Association Test and PLINK (genetic tool-set) to measure the parent-of-origin effect.

Results: Significant differences were found between affected individuals and the control group. In the case of the rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: Odds ratio [OR] 2.16 [95% CI 1.38-3.4]; mothers: OR 2.39 [95% CI 1.53-3.71]; and infants: OR 2.77 [95% CI 1.77-4.34]) and CP (fathers: OR 2.24 [95% CI 1.15-4.36] and infants: OR 2.43 [95% CI 1.25-4.7]). For CL±P and the rs7078160 risk allele, the phenotypes were: (fathers: OR 1.7 [95% CI 1.05-2.86]; mothers: OR 2.43 [95% CI 1.49-3.97]; and infants: OR 2.34 [95% CI 1.44-3.81]). In terms of consanguinity, we found significant association between consanguinity and the rs4752028 polymorphism minor allele among CL±P compared with controls (p = 0.001).

Conclusion: This is the first study to find a relationship between these two loci on 10q25 (rs4752028 and rs7078160) and NSOFC in a population with high levels of consanguinity.

Original languageEnglish
Pages (from-to)45-50
Number of pages6
JournalGenetic Testing and Molecular Biomarkers
Issue number1
Early online date11 Jan 2019
Publication statusPublished - 11 Jan 2019


  • cleft lip
  • cleft palate
  • consanguinity
  • etiology
  • VAX1
  • Genetic Testing
  • Humans
  • Genetic Predisposition to Disease/genetics
  • Infant
  • Male
  • Case-Control Studies
  • Saudi Arabia
  • Polymorphism, Single Nucleotide/genetics
  • Adult
  • Female
  • Cleft Palate/genetics
  • Infant, Newborn
  • Genome-Wide Association Study
  • Genotype
  • Transcription Factors/genetics
  • Genetic Heterogeneity
  • Phenotype
  • Alleles
  • Homeodomain Proteins/genetics
  • Family
  • Cleft Lip/genetics
  • Consanguinity
  • Brain/abnormalities

ASJC Scopus subject areas

  • Genetics(clinical)


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