Search

Objective: The goal of the present work was to use dental conditions that have been independently associated with cleft lip and palate (CL/P) as a tool to identify a broader collection of individuals to be used for gene identification that lead to clefts., Study Design: We studied 1573 DNA samples combining individuals that were born with CL/P or had tooth agenesis, supernumerary teeth, molar incisor hypomineralization, or dental caries with the goal to identify genetic associations. We tested 2 single-nucleotide polymorphisms that were located in the vicinity of regions suggested to contribute to supernumerary teeth. Overrepresentation of alleles were determined for combinations of individuals as well as for each individual phenotypic group with an α of .05., Results: We determined that the allele C of rs622260 was overrepresented in all individuals studied compared with a group of unrelated individuals who did not present any of the conditions described earlier. When subgroups were tested, associations were found for individuals with hypomineralization., Conclusions: Although we did not test this hypothesis directly in the present study, based on associations reported previously, we believe that CL/P is actually a syndrome of alterations of the dentition, and considering it that way may allow for the identification of genotype-phenotype correlations that may be useful for clinical care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective : The aim of this work was to fine-map the region 6q23.1, which obtained suggestive linkage signal (logarithm of the odds [LOD] score = 2.22 under a recessive model) to cleft lip with or without cleft palate (CL±P) in our previous genome-wide linkage scan to identify possible genetic variants that may contribute to CL±P. Design : We used densely spaced markers spanning the entire 6q23.1 region to test for association with CL±P in a family cohort sample. Setting : Clinical information and DNA samples were obtained from families in the Philippines at their homes or primary health care clinics. Participants : The study sample consisted of 477 subjects (224 females and 253 males), segregating isolated CL±P, from 72 living in the same area in the Philippines. Main Outcome Measure : Overtransmission of alleles to persons born with CL±P. Results : We found statistical evidence of association between a marker of TULP4 (rs651333) with CL±P (P = .00007). Conclusions : Our results further support the linkage results for the chromosome 6q region and reveal a novel candidate gene for CL±P.

Objective: Previous studies suggest individuals born with oral clefts and their families have a higher susceptibility for cancer, which raises the hypothesis that these two conditions share common molecular pathways. This study evaluated the association between oral clefts and polymorphisms in genes that play a role in craniofacial and tumor development., Materials and Methods: Four hundred and ninety-seven subjects born with oral clefts and 823 unaffected subjects were recruited. Twenty-nine markers in 13 genes were genotyped by the Taqman method. Chi-square was used to compare allele and genotype frequencies. Bonferroni correction for multiple testing was used and the established alpha was 0.0003. This study also used logistic regression to test if genetic variants were associated with oral clefts using positive family history of cancer and age as covariates., Results: There was no association between family history of cancer and oral clefts (p = 0.51). None of the 1320 study participants had a diagnosis of cancer at the time of participation in the study. The marker rs4980700 in FGF3 was associated with oral clefts (p = 0.0002). Logistic regression analysis also provided evidence for gene-gene interaction between FGF3 (rs4980700) and PAX9 (rs2073242), increasing the risk for isolated oral clefts (p = 0.0003)., Conclusion: FGF3 is associated with oral clefts and may interact with PAX9.

Objective: Caries is a common disease in humans and has a multifactorial etiology. It has been suggested that children born with cleft lip and/or palate (CL/P) have a higher susceptibility to caries, but data from several independent cohorts does not support this assumption. Previous work from our group suggested DEFB 1 is associated with higher caries experience. Since it is suspected that children born with CL/P have the same risk factors predisposing them to caries as other children of the same ages, the aim was to test if DEFB 1 was associated with caries experience in children born with CL/P., Materials and Methods: Sixty-nine children born with CL/P (aged 2-12 years) were included. Twenty-seven males and seven females had cleft lip and palate (CLP), six males and seven females had cleft lip (CL) and 13 males and nine females had cleft palate (CP). Caries was evaluated with the DMFT/dmft index by a calibrated evaluator. Two single nucleotide polymorphisms in DEFB 1 were selected (rs11362 and rs1800972) based on being associated with higher caries experience in previous work. Genotyping were carried out by real-time PCR using the Taqman assay method. The statistical analysis was performed between 'low-to-moderate caries experience group' and the 'high caries experience group'. Odds ratio calculations between caries experience and variant alleles and chi-square of Fisher exact tests at a level of significance of 0.05 were used., Results: There was no significant difference for caries experience between cleft types (p = 0.551). An association was found for the marker rs11362 and genotype distribution (p = 0.047). When analyzed in a recessive model, the genotype GG in this polymorphism increased the risk for caries susceptibility by more than 3-times (p = 0.031; OR = 3.16; 95% CI = 0.97-10.62)., Conclusion: The genetic variant rs11362 in DEFB 1 influences caries susceptibility in CL/P children. The results support the hypothesis that expression of DEFB 1 in saliva may serve as a biomarker for future caries risk.

Objective: To evaluate the association between AXIN2, CDH1 and IRF6 with oral clefts in a cohort from Latvia., Material and Methods: 283 unrelated individuals, 93 born with isolated oral clefts and 190 individuals born without any structural abnormalities were evaluated. Cleft type and dental anomalies outside the cleft area were determined by clinical examination. Four SNPs were selected for this study: rs2240308 and rs11867417 in AXIN2; rs9929218 in CDH1; and rs642961 in IRF6. Genotypes were determined by polymerase chain reaction using the Taqman assay method from a genomic DNA sample extracted from whole blood. Allele and genotype frequencies were compared between individuals born with or without oral clefts using the PLINK program., Results: Tooth agenesis was the most frequent dental anomaly found among individuals born with oral clefts (N=10; frequency 10.8%). The allele A in the IRF6 marker rs642961 was associated with all combined types of oral clefts (OR=1.74; CI 95% 1.07-2.82) and with cases with cleft lip with or without cleft palate (OR=1.88, CI 95% 1.15-3.01; p=0.007)., Conclusions: The IRF6 AP-2a binding site promoter polymorphism is associated with isolated oral clefts in Latvia.

Individuals with clefts present considerably more dental anomalies than individuals without clefts. We also have shown that these individuals report cancer in their families more often than do unaffected individuals. We investigated how these conditions correlated with genetic variants associated with clefts to ascertain if specific molecular signatures exist that could help identify individuals at risk for having offspring with these defects. We examined 573 individuals, 158 with clefts, 254 unaffected family members, and 161 non-related controls. Several clinical features, such as laterality, the presence of dental anomalies, medical history, and pregnancy history, were used to assess each individual's cleft status. Then, we performed molecular studies with genes that have been independently associated with oral clefts. We analyzed two datasets: nuclear families and case-control individuals where the case was the child from the family and controls were unrelated non-clefted individuals. In the family data, we confirmed association between clefts and rs987525 on chromosome 8 (p = 0.007) and found an association with rs987525 and tooth agenesis (p = 0.0003). In the case-control data, clefts, supernumerary teeth and familial cancer history were associated with ABCA4-rs481931 on chromosome 1 (p = 2E-19, 0.0007, 2E-06, respectively), and clefts and microdontia were associated with rs1325474 on chromosome 6 (p = 1E-06, 0.0002, respectively).