No Evidence for Linkage and Association between 4q Microsatellite Markers and Nonsyndromic Cleft Lip and Palate in Chilean Case-Parents Trios

2005 ◽  
Vol 42 (3) ◽  
pp. 267-271 ◽  
Author(s):  
Rafael Blanco ◽  
José Suazo ◽  
JoséLuis Santos ◽  
Hernán Carreño ◽  
Hernán Palomino ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Microsatellite Markers ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Statistical Significance ◽  
P Value ◽  
Genetic Trait ◽  
Multiple Alleles ◽  
Cleft Lip Palate

Objective Nonsyndromic cleft lip/palate (NSCLP) has the characteristics of a complex genetic trait. Linkage and association studies have suggested that one or more clefting loci may be located on chromosome 4q. The goal of this study was to evaluate the possible linkage and association due to linkage disequilibrium between five microsatellite markers located on 4q28 to 4q33 and NSCLP, using the case-parent trio design. Subjects and Methods A total of 56 Chilean families (32 simplex and 24 multiplex) were recruited. Microsatellite markers were analyzed using polymerase chain reaction with fluorescent-labeled forward primers, followed by electrophoresis on a laser-fluorescent sequencer. Case-parents trios were ascertained to assess linkage and linkage disequilibrium through a multistage procedure. Transmission disequilibrium tests for multiple alleles were carried out to assess the statistical significance of 4q28 to 4q33 microsatellite markers. Results Only weak evidence for linkage was obtained for the FGA marker (asymptotic uncorrected p value = .08 and empirical p value = .05). Only the FGA and UCP1 markers were selected for association analysis in trios, with unrelated cases achieving a nearly significant result for the UCP1 marker (asymptotic uncorrected p value = .07 and empirical p value = .19). Conclusion Though the FGA and UCP1 markers showed nearly significant p values for linkage and association, respectively, the results of the present study provided insufficient evidence of the existence of a major susceptibility locus in the 4q region that was analyzed in the present study.

Linkage Disequilibrium between MSX1 and Non-syndromic Cleft Lip/Palate in the Chilean Population

2004 ◽  
Vol 83 (10) ◽  
pp. 782-785 ◽  
Author(s):  
J. Suazo ◽  
J.L. Santos ◽  
H. Carreño ◽  
L. Jara ◽  
R. Blanco
Keyword(s):  
Linkage Disequilibrium ◽  
Cleft Lip ◽  
Association Studies ◽  
Genetic Trait ◽  
Multiple Alleles ◽  
Preferential Transmission ◽  
Cleft Lip Palate ◽  
Polymerase Chain ◽  
Complex Genetic Trait ◽  
Chilean Population

Non-syndromic cleft lip/palate (NSCLP) is a complex genetic trait. Linkage and association studies have suggested that a clefting locus could be located on chromosome 4p. Sixty Chilean families were recruited for this study; from these, we used unrelated trios to evaluate the possible linkage disequilibrium between MSX1 and NSCLP. An intragenic marker, MSX1-CA, and an extragenic marker, D4S432 at a distance of 0.8 cM from MSX1, were analyzed by means of polymerase chain-reaction with fluorescent-labeled forward primers, followed by electrophoresis on a laser-fluorescent sequencer. We carried out a transmission/disequilibrium test (TDT) for multiple alleles to evaluate the presence of linkage disequilibrium. Results showed a preferential transmission of the 169-bp allele of MSX1 (p = 0.03). Although there was no preferential transmission for the D4S432 marker, the overall extended TDT (ETDT) showed a significant result (p = 0.01). The authors’ findings support the hypothesis of the contribution of MSX1 in the etiology of NSCLP in the Chilean population.

scholarly journals A Rare Interstitial Duplication of 8q22.1–8q24.3 Associated with Syndromic Bilateral Cleft Lip/Palate

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Regina Ferreira Rezek ◽  
Ana Angélica Rodrigues Abbas ◽  
Juliana Forte Mazzeu ◽  
Siliana Maria Duarte Miranda ◽  
Cibele Velloso-Rodrigues
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Balanced Translocation ◽  
Genome Wide ◽  
Interstitial Duplication ◽  
Bilateral Cleft Lip ◽  
Cleft Lip Palate ◽  
Balanced Translocations

We present a rare case of 8q interstitial duplication derived from maternal balanced translocations in a patient with bilateral cleft lip and palate in syndromic form associated with other congenital malformations. G-banding cytogenetic analysis revealed a chromosomal abnormality in the form of the karyotype 46,XX der(22)t(8;22)(q22.1;p11.1)mat. Chromosome microarray analysis evidenced a 49 Mb duplicated segment of chromosome 8q with no pathogenic imbalances on chromosome 22. Two siblings also carry the balanced translocation. We have compared this case with other “pure” trisomies of 8q patients reported in the literature and with genome wide association studies recently published. This work highlights the involvement of chromosome 8q in orofacial clefts.

scholarly journals Case–Parent Trio Studies in Cleft Lip and Palate

2020 ◽  
Vol 07 (03) ◽  
pp. 075-079
Author(s):  
Mahamad Irfanulla Khan ◽  
Prashanth CS
Keyword(s):  
Genetic Variants ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Geographical Location ◽  
Genetic Association Studies ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Family Based ◽  
Study Designs

AbstractCleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case–control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case–parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case–parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

scholarly journals Alveolar cleft and maximum cleft width as predictors for difficult laryngoscopy and intubation in patients with unilateral complete cleft lip and palate

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Gamal A. Abdelhameed ◽  
Wael A. Ghanem ◽  
Simon H. Armanios ◽  
Tamer Nabil Abdelrahman
Keyword(s):  
Body Weight ◽  
Odds Ratio ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Difficult Laryngoscopy ◽  
Secondary Outcome ◽  
Pediatric Airway ◽  
Alveolar Cleft ◽  
Cleft Lip Palate ◽  
Width Measurements

Abstract Background Cleft lip and palate is one of the commonest congenital anomalies, which have an impact on feeding, speech, and dental development away from the significant psychosocial sequel. Early surgical repair aims to restore appearance and function, and the modern techniques can leave many defects undetectable. Therefore, the anesthetic challenge facing the pediatric airway with such abnormalities is still of a great impact. The aim of our study among 189 patients enrolled is to correlate alveolar gap and maximum cleft width measurements as predictors of difficult laryngoscopy and intubation in infants with unilateral complete cleft lip/palate aging from 1 to 6 months. As a secondary outcome, their weight is to be correlated too as another parameter. Results The alveolar gap and maximum cleft width are both of equal high predictive power (p value ≤ 0.001) with 100% sensitivity for both and specificity of 76.10% and 82.39% respectively, with a cut off value of ≤ 10 mm and 11 mm for these dimensions respectively, and odds ratio of incidence of difficult intubation is 4.18 and 5.68 respectively, while body weight ≤ 5.75 kg has an odds ratio of 2.32. Conclusion Alveolar cleft and maximum cleft width can be used as predictors for anticipation of difficult laryngoscopy and intubation infant patients with unilateral complete cleft lip and palate, while body weight ≤ 5.75 kg increases the risk more than twice.

scholarly journals Challenges of Adjusting Single-Nucleotide Polymorphism Effect Sizes for Linkage Disequilibrium

2021 ◽  
pp. 1-11
Author(s):  
Valentina Escott-Price ◽  
Karl Michael Schmidt
Keyword(s):  
Linkage Disequilibrium ◽  
Association Studies ◽  
Statistical Significance ◽  
Ordinary Least Squares ◽  
Effect Sizes ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Tikhonov Regularisation

<b><i>Background:</i></b> Genome-wide association studies (GWAS) were successful in identifying SNPs showing association with disease, but their individual effect sizes are small and require large sample sizes to achieve statistical significance. Methods of post-GWAS analysis, including gene-based, gene-set and polygenic risk scores, combine the SNP effect sizes in an attempt to boost the power of the analyses. To avoid giving undue weight to SNPs in linkage disequilibrium (LD), the LD needs to be taken into account in these analyses. <b><i>Objectives:</i></b> We review methods that attempt to adjust the effect sizes (β<i>-</i>coefficients) of summary statistics, instead of simple LD pruning. <b><i>Methods:</i></b> We subject LD adjustment approaches to a mathematical analysis, recognising Tikhonov regularisation as a framework for comparison. <b><i>Results:</i></b> Observing the similarity of the processes involved with the more straightforward Tikhonov-regularised ordinary least squares estimate for multivariate regression coefficients, we note that current methods based on a Bayesian model for the effect sizes effectively provide an implicit choice of the regularisation parameter, which is convenient, but at the price of reduced transparency and, especially in smaller LD blocks, a risk of incomplete LD correction. <b><i>Conclusions:</i></b> There is no simple answer to the question which method is best, but where interpretability of the LD adjustment is essential, as in research aiming at identifying the genomic aetiology of disorders, our study suggests that a more direct choice of mild regularisation in the correction of effect sizes may be preferable.

scholarly journals How is the face formed and when it goes wrong: In relation to Cleft Lip/Palate

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Fozia Khan
Keyword(s):  
Cleft Lip ◽  
Normal Development ◽  
Cleft Lip And Palate ◽  
Complex Structure ◽  
First Trimester ◽  
Facial Defect ◽  
Facial Defects ◽  
The Face ◽  
Embryonic Life ◽  
Cleft Lip Palate

The normal development of the face relies upon the correct morphogenesis of structures in utero that usually occurs within the first trimester of embryonic life. The face is a very complex structure involving many genes and factors and with it being such a crucial part of life, both physically and aesthetically and therefore mentally, its important for everything to be just right. However, when the normal process doesn’t go to plan this results in dysmorphogenesis, which cleft lip and palate (CLP) is an example of as the lip/palate doesn’t fuse together and the infant is left with a gap. Although the exact cause of CLP is unknown, it is thought to be a mixture of genetics, environment and the teratogens the mothers are exposed to within the environment. This report will demonstrate the normal development of the face for the purpose of understanding how it goes wrong, resulting in CLP. Since there is still a lot to be understood about CLP it will also shed light on recent advances in relating SHH and certain genes as a possible cause for this dysmorphogenesis. The report will also briefly look at the relation of CLP with the genes associated with syndromic and non-syndromic diseases and the different types of CLP. There are many other facial defects that are a result of dysmorphogenesis, however as CLP is one of the most common yet poorly understood facial defect, it will be the main focus of this report.

Birth Weight, Body Length, and Cranial Circumference in Newborns with Cleft Lip or Palate

1998 ◽  
Vol 35 (3) ◽  
pp. 255-261 ◽  
Author(s):  
Magnus Becker ◽  
Henry Svensson ◽  
Bengt Källén
Keyword(s):  
Birth Weight ◽  
Body Length ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Statistical Significance ◽  
The Body ◽  
Control Subjects ◽  
Study Population ◽  
Isolated Cleft Palate ◽  
Pierre Robin

Objective This paper reports on birth weight, body length, body mass index, and cranial circumference at birth of infants with cleft lip and/or palate born between 1973 and 1992. Methods Data were obtained from two nationwide swedish health registries. Infants with syndromes, twins, and infants with immigrant parentage were excluded from the study. Comparisons were made with all singleton births with the same exclusion criteria (n = 2,031,140). Results The body dimensions of infants with isolated cleft lip (n = 865) were found not to differ from those of control subjects, but infants with isolated cleft palate (n = 811) or cleft lip and palate (n = 1139) were found to be lighter and shorter than control subjects. Also, infants with the Pierre Robin sequence (n = 121) had a tendency to be lighter and shorter than control subjects, but these differences did not reach statistical significance despite the large study population.

Association between 10 Microsatellite Markers and Nonsyndromic Cleft Lip Palate in the Chilean Population

2004 ◽  
Vol 41 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Rafael Blanco ◽  
José Suazo ◽  
JoséLuis Santos ◽  
Mónica Paredes ◽  
Hsiao Sung ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Statistical Significance ◽  
Positive Family History ◽  
Case Control ◽  
University Hospital ◽  
Control Group ◽  
Exact Test ◽  
Rehabilitation Centers ◽  
Cleft Lip Palate ◽  
Chilean Population

Objective The objective of this case-control study was to evaluate the possible association between nonsyndromic cleft lip/palate (NSCLP) and 10 genetic markers in four chromosomal regions in the admixed Spanish-Amerindian Chilean population. Setting Study participants included 56 patients with NSCLP identified and interviewed for positive family history during the course of clinical examinations at different rehabilitation centers in the cities of Santiago and Talca, Chile. A control group of 59 normal individuals without known familial antecedents of clefting was obtained from blood bank donors of the University Hospital, University of Chile. Cases and controls belonged to low- to low-middle socioeconomic strata. Results Ten markers from chromosome 4p, 4q, 6p, 17q, and 19q were assessed (MSX1, D4S175, D4S192, F13A1, EDN1, D6S89, D6S105, D6S109, D17S579, BCL3). Four of them showed significant deviations from Hardy-Weinberg expectations in controls, according to the exact test (D4S192, BCL3, F13A1, and D6S89). The case-control comparison by means of the CLUMP program showed significant differences only in BCL3, and D6S109 almost reached statistical significance. Conclusions Most of the genetic regions with positive results in Caucasian populations may not be involved in NSCLP in Chile, regardless of the positive evidence for the candidate region on chromosome 19. Similar findings have been reported recently in the Chinese population.

Prevalence of Cleft Lip/Palate in the Fangshan District of Beijing, 2006-2012

2018 ◽  
Vol 55 (9) ◽  
pp. 1296-1301 ◽  
Author(s):  
Yanfen Yang ◽  
Hui Liu ◽  
Ruixin Ma ◽  
Lei Jin
Keyword(s):  
Data Analysis ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Upward Trend ◽  
Live Births ◽  
Cleft Lip Palate ◽  
Obstetric Services ◽  
Permanent Residents ◽  
Beijing China

Objective: To estimate the cleft lip with or without cleft palate (CL/P) prevalence among births between 2006 and 2012 in Fangshan district of Beijing, China. Design: Surveillance data analysis. Setting: All hospitals that provide obstetric services in the district. Patients: The CL/P cases presented for this report were from 13 weeks’ gestation to 7 days postpartum. Main Outcome Measures: The CL/P prevalence was defined as the number of cases per 10 000 births, including live births and stillbirths at 28 weeks’ gestation or beyond. Results: The overall CL/P prevalence was 18.9 (95% confidence interval [CI]: 15.1-22.7) per 10 000 births. From 2006 to 2012, the CL/P prevalence was 19.3, 20.2, 10.9, 16.1, 17.5, 25.4, and 22.3 per 10 000 births; annually, no significant change was noted ( Pfor trend = .311). The prevalence of cleft palate, cleft lip, and cleft lip and palate were 3.4 (95% CI: 2.0-5.4), 6.2 (95% CI: 4.2-8.8), and 9.4 (95% CI: 6.9-12.4) per 10 000 births, respectively. The CL/P prevalence among the nonpermanent residents (31.4 per 10 000 births) was 2.31 times that of permanent residents (13.6 per 10 000 births). Among nonpermanent residents, the CL/P prevalence showed an upward trend over the study period ( Pfor trend = .036), that increased from 38.8 (95% CI: 16.5-76.6) per 10 000 births in 2006 to 54.6 (95% CI: 25.7-100.4) per 10 000 births in 2012. Conclusions: The overall CL/P prevalence was stable in the Fangshan district. However, the CL/P prevalence of the nonpermanent residents increased significantly.

A Comparison of Three Methods of Repairing the Hard Palate

2002 ◽  
Vol 39 (4) ◽  
pp. 383-391 ◽  
Author(s):  
R. W. Pigott ◽  
E. H. Albery ◽  
I. S. Hathorn ◽  
N. E. Atack ◽  
A. Williams ◽  
...  
Keyword(s):  
Hard Palate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Small Sample Size ◽  
Statistical Significance ◽  
Small Sample ◽  
Velopharyngeal Insufficiency ◽  
Strong Trend ◽  
Computer Based ◽  
Palate Repair

Objective To compare growth, speech, and nasal symmetry outcomes of three methods of hard palate repair. Patients Consecutive available records of children born with unilateral bony complete cleft lip and palate over the period 1972 to 1992. Interventions Identical management of lip, nose, alveolus, and soft palate. Hard palate repair by Cuthbert Veau (CV) from 1972 to 1981, von Langenbeck (vL) from 1982 to 1989, or medial Langenbeck (ML) from 1989 to 1991. Outcome Measures For growth: GOSLON yardstick or 5-year model index. For speech: articulation test. Nasal anemometry. For nasal symmetry: Coghlan computer-based assessment. All these measures were developed during the period of data collection but not for this project. Results There was a strong trend toward more favorable anteroposterior maxillary growth with the change from CV to vL to ML techniques. This fell short of statistical significance because of the small sample size. There was a significant reduction in cleft-related articulation faults (p = .01) considered to be related to improved arch form. In the absence of improved rates of velopharyngeal insufficiency or nasal symmetry, increased surgical experience was discounted as a significant contribution to improved growth and articulation outcomes. Conclusions Reduced periosteal undermining and residual exposed palatal shelf from CV to vL to ML improved incisor relationships and articulation.

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