Nonsyndromic cleft lip with or without cleft palate in arab populations: genetic analysis of 15 risk loci in a novel case-control sample recruited in Yemen.

BACKGROUND: Nonsyndromic orofacial clefting (nsOFC) is among the most common of all congenital disorders and has a genetically complex etiology. Based on embryological and epidemiological data, the phenotype can be differentiated into nonsyndromic cleft lip with or without cleft palate (nsCL/P) and nonsyndromic cleft palate only, with nsCL/P being the most frequent form. Recent genetic research, predominantly performed in populations from Europe and Asia, has identified numerous genetic susceptibility loci for nsCL/P. As only few data are available concerning genetic susceptibility to nsCL/P in Arab populations, we investigated a newly recruited nsOFC sample from Yemen. METHODS: For each of the 15 currently known nsCL/P risk loci, the top single-nucleotide polymorphism (plus nine back-up variants) were genotyped in 242 nsCL/P cases and 420 healthy controls. RESULTS: Single-marker association analysis revealed significant associations for four loci (8q24, 9q22, 10q25, 13q31). The strongest association was for the European high risk locus at 8q24 (Pcorrected = 5.09 × 10(-4) ; heterozygous odds ratio = 1.74 (1.22-2.47), homozygous odds ratio = 2.47 (1.55-3.93). Five additional loci (1q32.2, 3q12, 8q21, 17q22, 20q12) showed nominal significance that did not withstand correction for multiple testing. Although the six remaining loci (1p22, 1p36, 2p21, 3p11, 15q22, 17p13) failed to reach nominal significance, the risk alleles were in the same direction as in the discovery studies. CONCLUSION: The results suggest that four of the 15 analyzed nsCL/P risk loci which were identified in European and Asian ethnicities significantly confer risk for nsCL/P in Arab populations.

Centre-based statistics of cleft lip with/without alveolus and palate as well as cleft palate only patients in Aden, Yemen.

OBJECTIVE: The purpose of the study was to report the types and patterns of cleft lip with/without cleft alveolus and palate as well as cleft palate only as seen in Aden, Yemen. DESIGN AND SETTING: Retrospective, centre-based study conducted at the Cleft Lip and Palate Centre, Aden University, Yemen. MATERIAL AND METHODS: Statistical evaluation of the data from all cleft patients who were registered at or referred to this centre during the years 2005-2011. RESULTS: A total of 1110 cleft patients were seen during the period studied (2005-2011). Amongst these there were 183 (16.48%) with a cleft lip and 144 (12.98) with a cleft of lip and alveolus, 228 (20.54%) had a cleft palate, and 555 (50%) had a combination of cleft lip, alveolus, and palate. The clefts were found more often in males than in females (56.5% boys versus 43.5% girls). This difference was statistically significant (p ≤ 0.001). Statistically significant sex differences were also noted when evaluating the various cleft types. Isolated cleft palates were found most often in females. Among the cleft palate cases there were 102 (9.2%) with a cleft soft palate only. The ages of the patients were between one day and 40 years. Two hundred and one children (18%) had a positive family history of clefts. Among the risk factors considered in this study, consanguineous marriages among cousins were found most frequently (in 48% of the cases). In contrast to this, only 10% of the mothers had reported to have been taking medication directly prior to or during the first trimester of their pregnancy. On average the mothers were neither very young nor very old. CONCLUSION: The prevalence rate of orofacial cleft types among this Yemeni sample was similar to prevalence rates previously reported in white Caucasians. The present study did neither find many cases with medication before, nor during, pregnancy; there were few young or very old mothers; and the incidence of positive family histories was similar to those found in other studies on clefts. However, consanguineous marriages were encountered quite often.