Lorena Castro Mariano

Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Brazilian population with high African ancestry

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is the most common orofacial birth defect, exhibiting variable prevalence around the world, often attributed to ethnic and environmental differences. Linkage analyses and genome‐wide association studies have identified several genomic susceptibility regions for NSCL ± P, mostly in European‐derived or Asian populations. Genetic predisposition to NSCL ± P is ethnicity‐dependent, and the genetic basis of susceptibility to NSCL ± P likely varies among populations. The population of Brazil is highly admixed, with highly variable ancestry; thus, the genetic determinants of NSCL ± P susceptibility may be quite different. This study tested association of 8 single‐nucleotide polymorphisms (SNPs), previously identified by genome‐wide studies in other populations, with NSCL ± P in a Brazilian population with high African ancestry. SNPs rs560426, rs642961, rs1530300, rs987525, rs3758249, rs7078160, rs17085106, and rs13041247 were genotyped in 293 Brazilian patients with NSCL ± P and 352 unaffected Brazilian controls. Each sample was also genotyped for 40 biallelic short insertion/deletion polymorphic markers to characterize genetic ancestry. The average African ancestry background was 31.1% for the NSCL ± P group and 36.7% for the control group. After adjustment for ancestry and multiple testing, the minor alleles of rs3758249 (OR: 1.58, 95% CI: 1.25–2.01, P = 0.0001) and rs7078160 (OR: 1.59, 95% CI: 1.21–2.07, P = 0.0002) were significantly associated with risk of NSCL ± P. Polymorphisms located in IRF6 (rs642961) and 8q24 (rs1530300 and rs987525) showed marginal associations in this Brazilian population with high African ancestry. These results indicate that rs3758249 at 9q22 and rs7078160 at 10q25.3 represent risk loci for NSCL ± P in the Brazilian population with high African ancestry.

Dental Anomalies in a Brazilian Cleft Population

Objective The aim of this study was to radiographically investigate the prevalence of dental anomalies outside the cleft area in a group of Brazilian patients with nonsyndromic cleft lip and/or palate (NSCL/P). Design, Participants, and Setting A retrospective analysis of 207 panoramic radiographs of patients with NSCL/P aged 12 to 45 years without history of tooth extraction and orthodontic treatment was performed. Results Dental anomalies were found in 75.4% of the patients, and tooth agenesis (29.2%) and supernumerary tooth (2.6%) were the most common anomalies. The risk of agenesis was higher among the individuals with cleft palate (CP) compared with individuals with cleft lip (CL) and cleft lip and palate (CLP) (agenesis: CP versus CL: odds ratio 6.27, 95% confidence interval 2.21-17.8, P = .0003; CP versus CLP: odds ratio 2.94; 95% confidence interval 1.27-6.81, P = .01). The frequency of dental agenesis was higher in patients with unilateral complete CLP (agenesis: P < .0001), incomplete bilateral CLP (agenesis: P = .0013), complete CP (agenesis: P < .0001), and incomplete CP (agenesis: P < .0001). The frequency of supernumerary teeth was higher in patients with bilateral complete CLP (P < .0001). The frequency of dental agenesis (P < .0001) and ectopic tooth (P = .009) was higher than the frequency estimated for general population. Conclusions The prevalence of dental anomalies in patients with NSCL/P was higher than that reported in overall population. This study found preferential associations between dental anomalies and specific extensions of NSCL/P, suggesting that dental agenesis and ectopic tooth may be part of oral cleft subphenotypes.