Background: Congenital heart defects (CHDs) are the most common congenital malformations, including structural malformations in the heart and great vessels. CHD complications such as low birth weight, prematurity, pregnancy termination, mortality, and morbidity depend on the type of defect.
Methods: In the present research, genetic analyses via whole-exome sequencing (WES) was performed on 3 unrelated pedigrees with CHDs. The candidate variants were confirmed, segregated by PCR-based Sanger sequencing, and evaluated by bioinformatics analysis.
Results: A novel stop-gain c.C244T:p.R82X variant in the FLT4 gene, as well as a nonsynonymous c.C1403T:p.T468M variant in the PTPN11 gene, was reported by WES. FLT4 encodes a receptor tyrosine kinase involved in lymphatic development and is known as vascular endothelial growth factor 3.
Conclusions: We are the first to report a novel c.C244T variant in the FLT4 gene associated with CHDs. Using WES, we also identified a nonsynonymous variant affecting protein-tyrosine phosphatase, the non-receptor type 11 (PTPN11) gene. The clinical implementation of WES can determine gene variants in diseases with high genetic and phenotypic heterogeneity like CHDs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737984 | PMC |
| http://dx.doi.org/10.1186/s40001-022-00920-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
VEGFR3 (FLT4) is crucial for embryonic lymphangiogenesis, and defects in this receptor can lead to congenital lymphedema type 1A (Milroy disease). This study analyses FLT4 gene sequence in 24 primary lymphedema patients, identifying genetic variants in five patients resembling typical Milroy disease. A novel likely pathogenic variant (c.
View Article and Find Full Text PDFChromosomal translocation resolves a diagnostic odyssey for familial Ruvalcaba syndrome.
Am J Med Genet A
January 2025
Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
In 1971, Ruvalcaba and colleagues reported a new syndrome in two brothers with severe intellectual disability, dysmorphic features, osseous dysplasia, and overlapping features in two intellectually disabled female maternal first cousins. No genetic cause was identified. We report on updated genomic studies and clinical follow-up in this family, including one of the original probands and their niece, whose own lifelong diagnostic odyssey had been unresolved for over four decades.
View Article and Find Full Text PDFA Mutation in the Familial Case of Primary Lymphedema: A Report.
Int J Mol Sci
May 2024
Institute of Cytology and Genetics, Lavrentyev Prospekt, 10, 630090 Novosibirsk, Russia.
Lymphedema is a disorder that leads to excessive swelling due to lymphatic insufficiency, resulting in the accumulation of protein-rich interstitial fluid. Primary lymphedema predominantly impacts the lower extremities and is frequently linked to hereditary factors. This condition is known to be associated with variants in several genes, such as , , and .
View Article and Find Full Text PDFFLT4 causes developmental disorders of the cardiovascular and lymphovascular systems via pleiotropic molecular mechanisms.
Cardiovasc Res
September 2024
Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine, and Health, Manchester Academic Health Science Centre, University of Manchester, 5th Floor, AV Hill Building, Oxford Road, Manchester, M13 9NT, UK.
Aims: Rare, deleterious genetic variants in FLT4 are associated with Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease. The distinct genetic variants in FLT4 are also an established cause of Milroy disease, the most prevalent form of primary hereditary lymphoedema. The phenotypic features of these two conditions are non-overlapping, implying pleiotropic cellular mechanisms during development.
View Article and Find Full Text PDFClinically relevant plasma proteome for adiposity depots: evidence from systematic mendelian randomization and colocalization analyses.
Cardiovasc Diabetol
April 2024
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: The accumulation of visceral and ectopic fat comprise a major cause of cardiometabolic diseases. However, novel drug targets for reducing unnecessary visceral and ectopic fat are still limited. Our study aims to provide a comprehensive investigation of the causal effects of the plasma proteome on visceral and ectopic fat using Mendelian randomization (MR) approach.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!