Editorial: Cleft Lip and Palate Anomalies/Syndromes.
Ontology highlight
ABSTRACT:
SUBMITTER: Alam MK
PROVIDER: S-EPMC9252325 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:We revisited 46 families with two or more siblings affected with an orofacial cleft that participated in previous genome wide studies and collected complete dental information. Genotypes from 392 microsatellite markers at 10 cM intervals were reanalyzed. We carried out four sets of genome wide analyses. First, we ran the analysis solely on the cleft status. Second, we assigned to any dental anomaly (tooth agenesis, supernumerary teeth, and microdontia) an affection status, and repeated the analysis. Third, we ran only the 19 families where the proband had a cleft with no dental anomalies. Finally, we ran only the 27 families that had a proband with cleft and additional dental anomalies outside the cleft area. Chromosomes (1, 2, 6, 8, 16, and 19) presented regions with LOD scores >2.0. Chromosome 19 has the most compelling results in our study. The LOD scores increased from 3.11 (in the scan of all 46 families with clefts as the only assigned affection status) to 3.91 when the 19 families whose probands present with no additional dental anomalies were studied, suggesting the interval 19p13.12-19q12 may contain a gene that contributes to clefts but not to dental anomalies. On the other hand, we found a LOD score of 3.00 in the 2q22.3 region when dental anomalies data were added to the analysis to define affection status. Our preliminary results support the hypothesis that some loci may contribute to both clefts and congenital dental anomalies. Also, adding dental anomalies information will provide new opportunities to map susceptibility loci for clefts.
| S-EPMC2570346 | biostudies-literature
Project description:Orofacial clefts are common birth defects and can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. There is substantial phenotypic diversity in individuals with these birth defects and their family members: from subclinical phenotypes to associated syndromic features that is mirrored by the many genes that contribute to the etiology of these disorders. Identification of these genes and loci has been the result of decades of research using multiple genetic approaches. Significant progress has been made recently due to advances in sequencing and genotyping technologies, primarily through the use of whole exome sequencing and genome-wide association studies. Future progress will hinge on identifying functional variants, investigation of pathway and other interactions, and inclusion of phenotypic and ethnic diversity in studies.
| S-EPMC3925974 | biostudies-literature
Project description:Nonsyndromic orofacial clefts are a common complex birth defect caused by genetic and environmental factors and/or their interactions. A previous genome-wide linkage scan discovered a novel locus for cleft lip with or without cleft palate (CL/P) at 9q22-q33. To identify the etiologic gene, we undertook an iterative and complementary fine mapping strategy using family-based CL/P samples from Colombia, USA and the Philippines. Candidate genes within 9q22-q33 were sequenced, revealing 32 new variants. Concurrently, 397 SNPs spanning the 9q22-q33 2-LOD-unit interval were tested for association. Significant SNP and haplotype association signals (P = 1.45E - 08) narrowed the interval to a 200 kb region containing: FOXE1, C9ORF156 and HEMGN. Association results were replicated in CL/P families of European descent and when all populations were combined the two most associated SNPs, rs3758249 (P = 5.01E - 13) and rs4460498 (P = 6.51E - 12), were located inside a 70 kb high linkage disequilibrium block containing FOXE1. Association signals for Caucasians and Asians clustered 5' and 3' of FOXE1, respectively. Isolated cleft palate (CP) was also associated, indicating that FOXE1 plays a role in two phenotypes thought to be genetically distinct. Foxe1 expression was found in the epithelium undergoing fusion between the medial nasal and maxillary processes. Mutation screens of FOXE1 identified two family-specific missense mutations at highly conserved amino acids. These data indicate that FOXE1 is a major gene for CL/P and provides new insights for improved counseling and genetic interaction studies.
| S-EPMC2778374 | biostudies-literature
Project description:The decision for lip revision surgery in patients with repaired cleft lip/palate is based on surgeons' subjective evaluation of lip disability. An objective evaluation would be highly beneficial for the assessment of surgical outcomes. In this study, the effects of lip revision on circumoral movements were objectively quantified. The hypothesis was that lip revision increases scarring and impairment. The study was a non-randomized clinical trial that included patients with cleft lip who had revision, patients with cleft lip who did not, and non-cleft control individuals. Three-dimensional facial movements were measured. Revision patients were measured before and after surgery. Other individuals were measured at similar intervals. Regression models were fit to summary measurements, and changes were modeled. Patients with repaired cleft lip/palate had fewer mean movements than control individuals. Lip revision did not worsen mean movements; however, individual patients' movements varied from 'improvement' to 'no change' to 'worse' relative to those of control individuals.
| S-EPMC2967701 | biostudies-literature
Project description:ObjectiveWe conducted a comprehensive review of state laws and regulations that require private health insurance plans to cover the services needed by children born with cleft lip and/or cleft palate (CL/P). The goal is to better understand how states are reducing the barriers children with CL/P face when seeking recommended health care services.DesignWe identified all state laws and regulations mandating insurance coverage of services for children with CL/P by private insurance carriers from 1999 through 2017 using Westlaw legal database. We categorized laws and regulations into ten services: facial surgery (facial, corrective, reconstructive), oral surgery, orthodontics, dental care, habilitation/rehabilitation/speech therapy, prosthetic treatment, audiology, nutrition counseling, genetic testing, and psychological counseling. We also captured broad mandates indicating coverage for all necessary treatments.ResultsThere was a trend toward increased coverage of services for CL/P over time. In 1999, 27 states and Washington, DC did not have relevant laws or regulations. By 2017, there were 19 states without laws or regulations mandating services. The most common mandated service was facial surgery followed by habilitation/rehabilitation/speech therapy, orthodontics, dental care, and oral surgery. Nutrition, audiology, genetic testing and psychological counseling were rarely included in mandated services.ConclusionsStates vary widely in their requirements for coverage of services needed by children with CL/P in private health insurance plans. There has been an increase in mandates over the past two decades to cover services, although significant variation continues to exist across states.
| S-EPMC7357273 | biostudies-literature
Project description:Plasma microRNAs (miRNAs) have recently emerged as a new class of regulatory molecules that influence many biological functions. However, the expression profile of plasma microRNAs in nonsyndromic cleft palate (NSCP) or nonsyndromic cleft lip with cleft palate (NSCLP) remains poorly investigated. In this study, we used Agilent human miRNA microarray chips to monitor miRNA levels in three NSCP plasma samples (mixed as the CP group), three NSCLP plasma samples (mixed as the CLP group) and three normal plasma samples (mixed as the Control group). Six selected plasma miRNAs were validated in samples from an additional 16 CP, 33 CLP and 8 healthy children using qRT-PCR. Using Venn diagrams, distinct and overlapping dysregulated miRNAs were identified. Their respective target genes were further assessed using gene ontology and pathway analysis. The results show that distinct or overlapping biological processes and signalling pathways were involved in CP and CLP. Our study showed that the common key gene targets reflected functional relationships to the Notch, Wnt, phosphatidylinositol and Hedgehog signalling pathways. Further studies should examine the mechanism of the potential target genes, which may provide new avenues for future clinical prevention and therapy.
| S-EPMC5349912 | biostudies-literature
Project description:PURPOSE:We revisited 42 families with two or more cleft-affected siblings who participated in previous studies. Complete dental information was collected to test the hypothesis that dental anomalies are part of the cleft phenotype spectrum, and can provide new opportunities for identification of cleft susceptibility genes. METHODS:Genotypes from 1489 single nucleotide polymorphism markers located in 150 candidate genes/loci were reanalyzed. Two sets of association analyses were carried out. First, we ran the analysis solely on the cleft status. Second, we assigned affection to any cleft or dental anomaly (tooth agenesis, supernumerary teeth, and microdontia) and repeated the analysis. RESULTS:Significant over-transmission was seen for a single nucleotide polymorphism in ankyrin repeat and sterile alpha motif domain containing 6 (rs4742741, 9q22.33; P = 0.0004) when a dental anomaly phenotype was included in the analysis. Significant over-transmission was also seen for a single nucleotide polymorphism in ERBB2 (rs1810132, 17q21.1; P = 0.0006). In the clefts only data, the most significant result was also for ERBB2 (P = 0.0006). Other markers with suggestive P values included interferon regulatory factor 6 and 6q21-q23 loci. In contrast to the above results, suggestive over-transmission of markers in GART, DPF3, and neurexin 3 were seen only when the dental anomaly phenotype was included in the analysis. CONCLUSIONS:These findings support the hypothesis that some loci may contribute to both clefts and congenital dental anomalies. Thus, including dental anomalies information in the genetics analysis of cleft lip and palate will provide new opportunities to map susceptibility loci for clefts.
| S-EPMC2734954 | biostudies-literature
Project description:Non-syndromic cleft lip with or without palate (NSCL/P) is a frequent malformation of the facial region. Genetic variants (SNPs) within nineteen loci have been previously associated with NSCL/P in GWAS studies of European individuals. These common variant SNPs may have subtler effects on the morphology of the lip and face in unaffected individuals. Several studies have investigated the genetic influences on facial morphology using land-marking methods, but these landmarks are sparse in the lip region. The aim of this study is to assess for associations between the nineteen NSCL/P SNPs and normal lip phenotypes, using a detailed categorical scale. Three-dimensional laser scanned facial images were obtained of 4,747 subjects recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC) and genetic data was available for 3,643 of them. A polygenetic risk score (PRS) combining the nineteen NSCL/P SNPs was associated with V-shaped Cupid's bow (P = 3 × 10-4) and narrow philtrum (P = 2 × 10-4) phenotypes. Analysis of individual SNPs found strong evidence for association between rs227731 and skeletal II pattern (P = 5 × 10-6). This study finds that known NSCL/P SNPs affect lip phenotypes in the general population, and an increased PRS is associated with narrow philtrum and V-shaped Cupid's bow. However, the difference in NSCL/P PRS between people with and without certain lip features is unlikely to be great enough to serve as a useful marker of NSCL/P risk.
| S-EPMC6207999 | biostudies-literature
Project description:Cleft lip (CL) with/without cleft palate (CP) (hereafter CL/P) is the second most common congenital birth defect, affecting 7.94 to 9.92 children per 10,000 live births worldwide, followed by Down syndrome. An increasing number of genes have been identified as affecting susceptibility and/or as causative genes for CL/P in mouse genetic and chemically-induced CL and CP studies, as well as in human genome-wide association studies and linkage analysis. While marked progress has been made in the identification of genetic and environmental risk factors for CL/P, the interplays between these factors are not yet fully understood. This review aims to summarize our current knowledge of CL and CP from genetically engineered mouse models and environmental factors that have been studied in mice. Understanding the regulatory mechanism(s) of craniofacial development may not only advance our understanding of craniofacial developmental biology, but could also provide approaches for the prevention of birth defects and for tissue engineering in craniofacial tissue regeneration.
| S-EPMC9969970 | biostudies-literature
Project description:Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common complex birth defect. Periconceptional supplementation with folic acid, a key component in DNA synthesis and cell division, has reduced the birth prevalence of neural tube defects and may similarly reduce the birth prevalence of other complex birth defects including NSCLP. Past studies investigating the role of two common methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs), C677T (rs1801133) and A1298C (rs1801131), in NSCLP have produced conflicting results. Most studies of folate pathway genes have been limited in scope, as few genes/SNPs have been interrogated. Here, we asked whether variations in a more comprehensive group of folate pathway genes were associated with NSCLP, and were there detectable interactions between these genes and environmental exposures?Fourteen folate metabolism-related genes were interrogated using 89 SNPs in multiplex and simplex non-Hispanic white and Hispanic NSCLP families.Evidence for a risk association between NSCLP and SNPs in NOS3 and TYMS was detected in the non-Hispanic white group, whereas associations with MTR, BHMT2, MTHFS, and SLC19A1 were detected in the Hispanic group. Evidence for over-transmission of haplotypes and gene interactions in the methionine arm was detected.These results suggest that perturbations of the genes in the folate pathway may contribute to NSCLP. There was evidence for an interaction between several SNPs and maternal smoking, and for one SNP with gender of the offspring. These results provide support for other studies that suggest that high maternal homocysteine levels may contribute to NSCLP and should be further investigated.
| S-EPMC4098909 | biostudies-literature