Jeffrey Murray

..To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth...

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..However, not much is known about the long term effects of oral clefts on health and healthcare use of affected individuals. In this study, we evaluate the effects of oral clefts on hospital use throughout the lifespan...

..Detailing the placental tissue transcriptome could provide a valuable resource for genomic studies related to placental disease...

..This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America...

..Mutations and rearrangements in PLOD-1 are known to be prevalent in patients with Ehlers-Danlos syndrome, kyphoscoliosis type (type VI [EDVI]). Several of the same organ systems are involved in Rieger syndrome and EDVI...

..As other mortality and morbidity causes including infections, hygiene, prematurity, and nutrition are eradicated in less developed countries, the burden of birth defects will increase proportionally...

..Several intronic PITX2 mutations have been reported in Axenfeld-Rieger patients but their effects on gene expression have not been tested...

..Related work has provided further support for investigating the role of common environmental triggers as causal covariates...

..No etiologic sequence variants were found in the coding sequence of the PGR gene. This study suggests that genetic variation in the PGR gene of either the mother or the fetus may trigger preterm labor...

..An efficient assay has been designed for the detection of the presence of X and Y chromosomes, which can be applied to the studies of sex chromosome abnormalities or sample quality control...

..The study aimed at identifying predictors of multivitamin use during pregnancy in Brazil...

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..Mutations in CHD7 are not common in isolated clefting cases and we found minimal evidence that CHD7 can act as a modifier for non-syndromic clefting...

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..This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations...

..Until genotyping is available at a clinically prescriptive level, other predictors (eg, age and activity level) can be used to tailor pain-relieving strategies for children undergoing needle sticks...

..To evaluate the outcomes of care for children by type of oral cleft...

..Given the similarities between Van der Woude syndrome and isolated cleft of the lip and/or palate, the current study was designed to evaluate the pattern of cognitive function in adults with Van der Woude syndrome...

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..Our major goal was to determine if genetic risk factors play a role in patent ductus arteriosus seen in preterm infants...

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..003), AGTR1 (p = 0.005), TBX5 (p = 0.003), CETP (p = 0.004), and GP1BA (p = 0.005). Our data suggest that genetic risk factors contribute to the development of ROP...

..Our findings place IRF6 and AP-2alpha in the same developmental pathway and identify a high-frequency variant in a regulatory element contributing substantially to a common, complex disorder...

..The suggested ineffectiveness for pregnancies complicated with common birth defects deserves further research...

..Further research is needed to understand the effects of prenatal care use for pregnancies that are complicated with birth defects...

..The purpose of this article is to provide an overview of genetic approaches to identifying disease genes for genetically complex birth defects...

..We searched for a specific genetic factor contributing to this complex trait by examining large numbers of affected patients and families and evaluating a specific candidate gene...

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..The clustered pattern of HRQL values suggests either a consensus among evaluators of a limited burden of oral clefting or an overall lack of understanding of the evaluation task...

..Our objective was to evaluate in an exploratory framework the effects of prenatal use of folic acid and other dietary supplements on child development at around 3 years of life...

..Additionally, 15 NS CLP patients had a combination of coding mutations and CNE variants, suggesting that an accumulation of variants in the FGF signaling pathway may contribute to clefting...

..However, results from the paired sister study suggest the potential contribution of skewed XCI to orofacial clefting, particularly cleft lip and palate...

..CONCLUSIONS: Rare MSX1 mutations are found in some cases of cleft lip and/or cleft palate but others remain to be found most likely in other regulatory regions of the gene...

..These data indicate that FOXE1 is a major gene for CL/P and provides new insights for improved counseling and genetic interaction studies...

..The data suggest that the FGF signaling pathway may contribute to as much as 3-5% of NS CLP and will be a consideration in the clinical management of CLP...

..Arnt2 and Ahr proteins dimerize in vitro. TCDD exposure is also associated with orofacial clefting in children of parents involved in agricultural work...

..The stability of genomes we observed in our study samples also suggests that detection of discordant events in other monozygotic twin pairs would be remarkable and of potential disease significance...

..This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care...

..Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia...

..CONCLUSIONS: Given the lack of any novel genes near either breakpoint, changes in potential regulatory elements may be the best model to explain the loss of PITX2 expression in these patients and hence the Rieger's syndrome phenotype...

..These new SNPs found for the human TPO and TPOR genes help explain variations in blood PLT counts and may be useful in patient studies related to the roles of TPO and/or TPOR in disease...

..Together, these complementary strategies are providing researchers with new clues as to what mechanisms underlie orofacial clefting...

..CONCLUSION: Oral clefts occurrence is not correlated with increasing maternal age, and inclusion of data mixing isolated and syndromic cases can confound the analysis and must be avoided...

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..While no etiologic variants were identified in this study, sequence comparisons of discordant MZ twins can serve as a tool for identifying etiologic mutations in clefting and other complex traits...

..chagasi infection. The results preliminarily suggest that this may be the case, and follow-up with larger populations is needed for verification...

..Finally, this is the first report of a double mutation involving GLI2 and PTCH in the same patient...

..Despite prenatal diagnosis, shared myocardium or cardiac anomalies in CTS often determine the prognosis...

..These mutations are of particular interest because the C-terminus has both inhibitory and stimulatory activities...

..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...

..The effect of this TGFA genotype was even stronger among children homozygous for the MSX1-CA A4 allele, raising the possibility of interaction between these two genes...

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..CONCLUSIONS: The potential increase in power offered by the log-linear approach is offset by concerns regarding the validity of this approach when the independence assumption is violated...

..14, 6.78), and primary lung cancer among males born with both cleft lip and cleft palate (SIR = 2.49, 95% CI: 1.00, 5.14). The results do not provide evidence for an increased overall cancer risk for individuals born with oral clefts...

..Our simple methods to identify deletions and to determine the boundaries of a deletion would facilitate the identification of such patients...

..Information on the methods used and issues faced by the NBDPS may be of value to others considering the addition of DNA sampling to epidemiologic studies...

..The aim of this study is to determine the degree to which maternal age and paternal age independently influence the risk of having a child with oral clefts...

..CONCLUSIONS: MSX1 contributes to nonsyndromic clefting in a Vietnamese population, and consistent with other studies, identifiable mutations in this gene cause about 2% of cases of nonsyndromic clefting...

..This report presents summary statements of the four subcommittees...

..As samples and data become increasingly available, more effort is needed in designing innovative analytical methods to study gene-environment interactions...

..These results support our hypothesis that population-specific associations and population heterogeneity in dermatoglyphic patterns exist for CL/P cases and their relatives...

..113). Taken together, these findings further support a role for IRF6 variants in clefting of the lip and provide specific risk estimates in a Norwegian population...

..02, broad). Association with JAG2 improved from P = 0.09 under the narrow definition to P = 0.04 under the broad definition. Broadening the oral-facial cleft phenotype to include subclinical variants may improve power in genetic studies...

..014) and IRF6 (P = 0.002) markers. There were statistically significant data suggesting that IRF6 interacts not only with MSX1 (P = 0.001), but also with TGFA (P = 0.03)...

..7, 95% CI=0.2-15.7). In conclusion, we find little evidence of interaction between the child's genotypes at TGFA TaqI and various exposures for cleft palate, with the possible exception of folic acid intake...

..The purpose of this study was to determine whether the candidate genes previously studied in subjects with cleft lip, cleft palate, or both are associated with hypodontia outside the region of the cleft...

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..These findings suggest a possible role of MTHFR and folic acid in the causation of orofacial clefts, but the strength and direction of these effects remain to be clarified...

..0004). These are the first genomewide significant linkage results ever reported for CL/P, and they represent an unprecedented demonstration of the power of linkage analysis to detect multiple genes simultaneously for a complex disorder...

..3 and is deleted in all of the individuals tested so far who have this syndrome. Thus, SKI may contribute to some of the phenotypes common in 1p36 deletion syndrome, and particularly to facial clefting...

..The present study found an association between oral clefts and smoking and, although not conclusive, supports an association of oral cleft with alcohol...

..We attempted to replicate these findings and to conduct a candidate gene and locus evaluation of genetic involvement in common forms of myopia...

..Together these data suggest that both rare and common mutations within PVRL1 make a minor contribution to disrupting the initiation and regulation of cell-to-cell adhesion and downstream morphogenesis of the embryonic face...

..0, assuming homogeneity, was estimated at 93.2%. We found no confirmatory evidence of linkage between juvenile myopia and regions of chromosomes 12 and 18 previously associated with pathological myopia...

..One of our patients had a Thr1052Met mutation, holoprosencephaly-like facial features, and a normal MRI. Ming et al. [(2002); Hum Genet 110:297-301] reported an identical mutation, but with alobar holoprosencephaly...

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..between-Brazil-and-the-United-Statesi.to better-understand the effects,_oLbirtb-.defects_and^cranioiaciaLanomalies-jn-particular^on-maternaLfamily-units-and-to. decrease the burden of these defects directly. ..

..If we were to realize a 50% reduction in CLP in these families, in the US alone, we would decrease the personal burden on each individual child and family and save $100 million in cleft-related economic costs per year. ..

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..It will confirm proof of principle that complex human birth defects can be understood, and diagnosis and prevention improved. ..

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..In addition, the study could result in proof of principle that discordant MZ twins are powerful resources for gene and/or mechanism identification in studies of complex traits in general. ..

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..It will confirm proof of principle that complex human craniofacial disorders can be understood and diagnosis and prevention improved. ..

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..The major genes identified in the association and linkage analysis will then be characterized using fine structure genetic mapping and DNA sequencing techniques...

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