scholarly journals Functional analysis of candidate genes in 2q13 deletion syndrome implicates FBLN7 and TMEM87B deficiency in congenital heart defects and FBLN7 in craniofacial malformations

2014 ◽  
Vol 23 (16) ◽  
pp. 4272-4284 ◽  
Author(s):  
Mark W. Russell ◽  
Maide O. Raeker ◽  
Sarah B. Geisler ◽  
Peedikayil E. Thomas ◽  
Tracy A. Simmons ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Candidate Genes ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Deletion Syndrome ◽  
Craniofacial Malformations ◽  
2Q13 Deletion

Congenital heart defects in the recurrent 2q13 deletion syndrome

2021 ◽  
pp. 104381
Author(s):  
M.C. Digilio ◽  
M.L. Dentici ◽  
S. Loddo ◽  
L. Laino ◽  
G. Calcagni ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Deletion Syndrome ◽  
2Q13 Deletion

Abstract 2722: Large Scale Mutation Discovery Screen Identifies Functionally Variant UGDH Alleles in Patients with Atrioventricular Valve Defects

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jeroen Bakkers ◽  
Sonja Chocron ◽  
Victor Gouriev ◽  
Kelly Smith ◽  
Ronald Lekanne dit Deprez ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Large Scale ◽  
Heart Defects ◽  
Glucose Dehydrogenase ◽  
Model Organisms ◽  
Missense Mutations ◽  
Coding Regions

Background: Congenital heart defects are the most common birth defects. Although genetic dispositions are believed to cause CHDs, only few genes have been identified that harbour mutations causing such defects. Studies in model organisms have identified many essential genes for cardiac development. UDP-glucose dehydrogenase (UGDH) enzymatic activity is required for the signal transduction of FGF and Wnt ligands and zebrafish jekyll/ugdh mutations lack AV valves. Methods and Results: From literature candidate genes were selected that are essential for AV canal-, septum-, and valve formation. By large scale sequencing we analysed the coding regions of 36 candidate genes in 192 patients with reported AVSDs. As a result we identified 457 genetic variations of which 207 variants are in flanking non-coding regions, 156 variants are in coding regions but silent and 94 variants are non-synonymous variants that alter the protein sequence. Comparison with the available databases such as HapMap and screening 350 control individuals resulted in the validation of 49 non-synonomous missense mutations in 23 genes only present in the patient group. These included novel GATA4 missense mutations (R285C and M224V) located in the highly conserved DNA binding domains, which by in vitro analysis significantly reduce transcriptional activity of the protein. Three patients with mitral valvar prolapse and mitral regurgitation were identified with novel missense mutations in the UDP-glucose dehydrogenase (UGDH) gene (R141C and E416D). In vitro experiments demonstrated a negative affect on enzyme activity and stability by a change in protein conformation. Furthermore, experiments in zebrafish jekyll/ugdh mutants showed that UGDH R141C and UGDH E416D couldn’t rescue the defects in AV formation demonstrating an inactivating effect of these missense mutations in vivo. Conclusions: A model organism based candidate gene screen in CHD patients resulted in the identification of novel functional missense mutations in the UGDH gene not previously implicated in congenital heart defects.

Chromosome r(3)(p25.3q29) in a Patient with Developmental Delay and Congenital Heart Defects: A Case Report and a Brief Literature Review

2016 ◽  
Vol 148 (1) ◽  
pp. 6-13
Author(s):  
Kaihui Zhang ◽  
Fengling Song ◽  
Dongdong Zhang ◽  
Yong Liu ◽  
Haiyan Zhang ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Ring Chromosome ◽  
Deletion Syndrome ◽  
Facial Features ◽  
Whole Genome Microarray ◽  
Available Information ◽  
3P Deletion Syndrome

Ring chromosome 3, r(3), is an extremely rare cytogenetic abnormality with clinical heterogeneity and only 12 cases reported in the literature. Here, we report a 1-year-old girl presenting distinctive facial features, developmental delay, and congenital heart defects with r(3) and a ∼10-Mb deletion of chromosome 3pterp25.3 (61,891-9,979,408) involving 42 known genes which was detected using G-banding karyotyping and CytoScan 750K-Array. The breakpoints in r(3) were mapped at 3p25.3 and 3q29. We also analyzed the available information on the clinical features of the reported cases with r(3) and 3p deletion syndrome in order to provide more valuable information of genotype-phenotype correlations. To our knowledge, this is the largest detected fragment described in r(3) cases and the second r(3) study using whole-genome microarray.

Macrothrombocytopenia as diagnosis predictor of 22q11 deletion syndrome among patients with congenital heart defects

2015 ◽  
Vol 167 (6) ◽  
pp. 1406-1408 ◽  
Author(s):  
Patrícia Trevisan ◽  
Sílvia Barbosa ◽  
Graziela Sperotto ◽  
Caroline Costi ◽  
Reinaldo L. de Omena Filho ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Deletion Syndrome ◽  
22Q11 Deletion ◽  
22Q11 Deletion Syndrome

scholarly journals Screening for 22q11 deletion syndrome among patients with congenital heart defects

2014 ◽  
Vol 132 (2) ◽  
pp. 125-126 ◽  
Author(s):  
Rafael Fabiano Machado Rosa ◽  
Rosana Cardoso Manique Rosa ◽  
Patrícia Trevisan ◽  
Carla Graziadio ◽  
Marileila Varella-Garcia ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Deletion Syndrome ◽  
22Q11 Deletion ◽  
22Q11 Deletion Syndrome

scholarly journals Screening of 22q11.2DS Using Multiplex Ligation-Dependent Probe Amplification as an Alternative Diagnostic Method

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Sathiya Maran ◽  
Siti Aisyah Faten ◽  
Swee-Hua Erin Lim ◽  
Kok-Song Lai ◽  
Wan Pauzi Wan Ibrahim ◽  
...  
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Diagnostic Method ◽  
Heart Defects ◽  
22Q11.2 Deletion Syndrome ◽  
Confirmatory Test ◽  
Deletion Syndrome ◽  
Molecular Diagnostic ◽  
Nonallelic Homologous Recombination ◽  
Dependent Probe

Background. The 22q11.2 deletion syndrome (22q11.2DS) is the most common form of deletion disorder in humans. Low copy repeats flanking the 22q11.2 region confers a substrate for nonallelic homologous recombination (NAHR) events leading to rearrangements which have been reported to be associated with highly variable and expansive phenotypes. The 22q11.2DS is reported as the most common genetic cause of congenital heart defects (CHDs). Methods. A total of 42 patients with congenital heart defects, as confirmed by echocardiography, were recruited. Genetic molecular analysis using a fluorescence in situ hybridization (FISH) technique was conducted as part of routine 22q11.2DS screening, followed by multiplex ligation-dependent probe amplification (MLPA), which serves as a confirmatory test. Results. Two of the 42 CHD cases (4.76%) indicated the presence of 22q11.2DS, and interestingly, both cases have conotruncal heart defects. In terms of concordance of techniques used, MLPA is superior since it can detect deletions within the 22q11.2 locus and outside of the typically deleted region (TDR) as well as duplications. Conclusion. The incidence of 22q11.2DS among patients with CHD in the east coast of Malaysia is 0.047. MLPA is a scalable and affordable alternative molecular diagnostic method in the screening of 22q11.2DS and can be routinely applied for the diagnosis of deletion syndromes.

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