ABSTRACT
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.
Subject(s)
Brain/abnormalities , Cleft Lip/genetics , Cleft Palate/genetics , Homeodomain Proteins/genetics , Transcription Factors/genetics , Adult , Alleles , Case-Control Studies , Consanguinity , Family , Female , Genetic Heterogeneity , Genetic Predisposition to Disease/genetics , Genetic Testing , Genome-Wide Association Study , Genotype , Humans , Infant , Infant, Newborn , Male , Phenotype , Polymorphism, Single Nucleotide/genetics , Saudi ArabiaABSTRACT
OBJECTIVES: To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC) and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia. METHODS: All infants (114,035) born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133) were identified and data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants' pediatricians. Control infants (n=233) matched for gender and born in the same hospitals during the same period, were selected. RESULTS: The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL) was 0.47/1000 births, cleft lip and palate (CLP) was 0.42/1000 births, and cleft palate (CP) was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46), particularly for first cousin marriages. CONCLUSION: The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity.
