scholarly journals Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate

2010 ◽  
Vol 152A (7) ◽  
pp. 1701-1710 ◽  
Author(s):  
Ariadne Letra ◽  
Renato Menezes ◽  
Manika Govil ◽  
Renata F. Fonseca ◽  
Toby McHenry ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Chromosome Region ◽  
Association Studies ◽  
Cleft Lip Palate

Screening of IRF6 Variants in Patients Subjected to Genetic Association Studies for Nonsyndromic Cleft Lip/Palate

2020 ◽  
pp. 105566562098023
Author(s):  
José A. Velázquez-Aragón ◽  
Ariadna González-del Angel ◽  
Miguel A. Alcántara-Ortigoza ◽  
Miriam E. Reyna-Fabián ◽  
Bernardette Estandia-Ortega
Keyword(s):  
Association Study ◽  
Cleft Lip ◽  
Diagnostic Yield ◽  
Association Studies ◽  
Tertiary Care ◽  
Case Series ◽  
Case Control ◽  
Retrospective Case ◽  
Cleft Lip Palate ◽  
Control Association

Objective: To screen for interferon regulatory factor 6 (IRF6) pathogenic variants in patients clinically diagnosed with nonsyndromic cleft lip palate (NSCL/P) and establish the proportion of misdiagnosed Van der Woude syndrome (VWS) cases, which could have biased previous NSCL/P case–control association studies. Design: Retrospective case series. Setting: Tertiary care children’s hospital. Participants: One hundred seventy-two unrelated Mexican patients with NSCL/P, 128 of whom had previously been included in a NSCL/P case–control association study. Main Outcomes Measurements: Sanger sequencing of the 9 IRF6 exons were performed, all variants respect with sequence reference were reported and classified for their pathogenic significance according to the American College of Medical Genetics and Genomics guidelines. Results: Seven percent of cases were familial. No pathogenic variant was identified in IRF6. We identified 12 previously reported benign variants; their frequencies did not significantly differ from those reported for individuals of Mexican ancestry. Three of them were uncommon intronic variants not reported in ClinVar. The rs2235371 and rs2235375 variants, which were previously analyzed in a NSCL/P case–control association study (containing 132 patients, 128 of whom were analyzed herein) did not show discordant association results comparing to the 370 controls from the previous study. Conclusions: The misdiagnosis of IRF6-related VWS as NSCL/P appears to be infrequent in our sample, suggesting that mutational screening of IRF6 would have a low diagnostic yield in patients with NSCL/P. The absence of IRF6 pathogenic alleles could be related to the application of an exhaustive clinical evaluation that discarded the syndromic forms and/or the low proportion of familial cases included.

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.

Neonatal Care of Infants with Cleft Lip and/or Palate: Feeding Orientation and Evolution of Weight Gain in a Nonspecialized Brazilian Hospital

2007 ◽  
Vol 44 (3) ◽  
pp. 329-334 ◽  
Author(s):  
Lívia Gobby Amstalden-Mendes ◽  
Luis Alberto Magna ◽  
Vera Lúcia Gil-da-Silva-Lopes
Keyword(s):  
Weight Gain ◽  
Surgical Procedure ◽  
Cleft Lip ◽  
Tertiary Hospital ◽  
Postnatal Period ◽  
Rehabilitation Centers ◽  
Spontaneous Reports ◽  
Cleft Lip Palate ◽  
Feeding Resources

Objectives: To survey the feeding orientation received during the postnatal period by the parents of cleft babies, as well as the location where they receive the orientation; to identify resources used in feeding; and to assess the correlation of the child's weight with the surgical procedure schedule. Design: During consultation for diagnosis and genetic counseling in a general tertiary hospital, 26 parents of cleft babies born in different hospitals were interviewed based on a semistructured protocol and spontaneous reports. Results: Cleft palate was present in 42.31% (11/26), cleft lip/palate in 50% (13/26), and cleft lip in 7.69% (2/26) of the cases. Feeding orientation was given in maternities to 72% (18/25) and in specific rehabilitation centers to 24% (6/ 25) of the parents. Breast-feeding was encouraged in every case. Nevertheless, other feeding resources were necessary, especially bottles. Surgical procedure delays caused by poor weight gain occurred in 66.7% (12/18). Conclusions: Neonatal feeding orientation was not systematically given in every case. Because it is an important way to achieve an effective weight gain, educational programs for nonspecialized health professionals, as well as regular pediatric follow-up and specialized multi-professional teams, could improve nutritional intake and could move the schedule for surgical procedures forward. The results also suggest that specific neonatal health care for cleft babies should be part of health policy.

scholarly journals Detection of non-affine shape outliers for matched-pair shape data

2012 ◽  
Vol 51 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Stanislav Katina
Keyword(s):  
Outlier Detection ◽  
Large Scale ◽  
Cleft Lip ◽  
Scar Tissue ◽  
Matched Pair ◽  
Small Scale ◽  
Affine Subspaces ◽  
Cleft Lip Palate ◽  
Shape Data

ABSTRACT Cleft lip/palate (CLP) is a relatively common birth defect so dis- figuring that nowadays it is almost always corrected surgically as early as possible. The postnatal surgical correction does not, however, result in a normally growing upper jaw, but instead, owing to scar tissue, one that grows abnormally. It is important to decide if a clinical treatment group is homogeneous. The example involves data from digitally processed lateral X-ray films of 48 boys who have complete unilateral CLP but no other malformation. 22 landmarks were represented by their Procrustes shape coordinates, principal components of matched- pair differences were examined, and the distribution of the 48 shape changes was studied for outliers in the affine and non-affine subspaces of the full Procrustes shape and form space. To separate outliers from inliers we use bagplots. There are no outliers apparent in the affine subspace. In the non-affine subspaces, we found no outliers in the subspace of bending patterns at large scale but four out- liers in the subspace of local changes at small scale. Almost the same outliers were found by form-space PCA. These latter are associated with possible creases of the corresponding thin-plate splines. In those cases we can use the same spline formalism to relax the outlying form to an inlier by optimal relaxation along the curve d´ecolletage that weighs bending energy against Procrustes distance and stop relaxation on the fence. These maneuvers suggest a possibly novel and interesting fusion of the Procrustes-spline toolkit with outlier detection. They also have practical implications for craniofacial management of CLP follow-up as well as suggestive implications for outlier detection in applied craniometrics and anthropometrics more generally.

scholarly journals Whole-genome Sequencing Reveals De-novo Mutations Associated with Nonsyndromic Cleft Lip/Palate

2021 ◽  
Author(s):  
Waheed Awotoye ◽  
Peter A. Mossey ◽  
Jacqueline B. Hetmanski ◽  
Lord Jephthah Joojo Gowans ◽  
Mekonen A. Eshete ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Cleft Lip ◽  
De Novo ◽  
Association Studies ◽  
Whole Genome ◽  
Loss Of Function ◽  
De Novo Mutations ◽  
Pathogenic Variants ◽  
Cleft Lip Palate

Abstract The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact DNMs that contribute to the risk of nsCL/P, we conducted whole genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs that contribute to the risk of nsCL/P. These include novel loss-of-function DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Experimental evidence showed that ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, MINK1, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TTN genes contribute to facial development and mutations in these genes could contribute to CL/P. Association studies have identified TULP4 as a potential cleft candidate gene, while ARHGAP10 interacts with CTNNB1 to control WNT signaling. DLX6, EPHB2, SEMA3C and SEMA4D harbor novel damaging DNMs that may affect their role in neural crest migration and palatal development. This discovery of pathogenic DNMs also confirms the power of WGS analysis of trios in the discovery of potential pathogenic variants.

scholarly journals Novel missense mutation of the TP63 gene in a newborn with Hay-Wells/Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome: clinical report and follow-up

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Gregorio Serra ◽  
Vincenzo Antona ◽  
Mario Giuffré ◽  
Federica Li Pomi ◽  
Lucia Lo Scalzo ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Missense Mutation ◽  
Cleft Lip ◽  
Ectodermal Dysplasia ◽  
Clinical Signs ◽  
Clinical Report ◽  
Sequencing Analysis ◽  
Genetic Syndrome ◽  
Cleft Lip Palate

Abstract Introduction Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing. Patient’s presentation We hereby report on a female newborn with erythroderma, thin lamellar desquamations, extensive skin erosions, sparse and wiry hair, filiform ankyloblepharon adnatum, agenesis of the lachrymal puncta, cleft palate and nail dysplasia. Her phenotype was compatible with AEC syndrome. Then, based on the clinical suspicion, sequencing analysis of the TP63 gene was performed, and revealed a de novo novel missense mutation. Eyelids adherence and cleft palate underwent surgical correction, while skin erosions were treated with topical antibiotics/antifungals and emollient/re-epithelizing creams. A surgical reconstruction is presently planned for the agenesis of the lachrymal puncta. The infant currently is 17 months of age and is included in a multidisciplinary follow-up. At present shows growth impairment and mild developmental delay, and typical signs of ectodermal dysplasia with small areas of dermatitis lesions on the scalp, without further abnormalities. Conclusions Our report underlines the relevance of an early and careful clinical evaluation in neonates with ankyloblefaron, facial dysmorphism, and signs of ectodermal dysplasia. In these cases, the suspicion of AEC syndrome must be promptly raised, and sequencing analysis of TP63 early performed as well. An individualized, multidisciplinary and long-term follow-up should be guaranteed to affected subjects and their families, also to identify associated morbidities and prevent possible serious complications and adverse outcomes.

scholarly journals Feeling Normal? Long-Term Follow-up of Patients with a Cleft Lip–Palate after Rhinoplasty with the Derriford Appearance Scale (DAS-59)

2016 ◽  
Vol 32 (02) ◽  
pp. 219-224 ◽  
Author(s):  
Andreas Reichelt ◽  
Gilbert Nolst-Trenité ◽  
Dirk Menger ◽  
Andreas Albers
Keyword(s):  
Cleft Lip ◽  
Long Term Follow Up ◽  
Cleft Lip Palate

scholarly journals Geospatial Analysis of Risk Factors Contributing to Loss to Follow-up in Cleft Lip/Palate Care

2018 ◽  
Vol 6 (9) ◽  
pp. e1910 ◽  
Author(s):  
Banafsheh Sharif-Askary ◽  
Peter G. Bittar ◽  
Alfredo E. Farjat ◽  
Beiyu Liu ◽  
Joao Ricardo Nickenig Vissoci ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cleft Lip ◽  
Geospatial Analysis ◽  
Loss To Follow Up ◽  
Cleft Lip Palate
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