NRP1haploinsufficiency predisposes to the development of Tetralogy of Fallot

Autor: Carmen M. Warren, Jessica Tenney, Anna Sarukhanov, Maria Luisa Iruela-Arispe, Fabiana Csukasi, Ivan Duran, Deborah Krakow, Mark Skalansky
Rok vydání: 2018
Předmět:
0301 basic medicine
prenatal ultrasound
DNA Mutational Analysis
Gene Expression
Haploinsufficiency
Disease
neuropilin 1
0302 clinical medicine
Neuropilin 1
chromosomal deletion
Medicine
Genetics (clinical)
Ultrasonography
Tetralogy of Fallot
Comparative Genomic Hybridization
Single Nucleotide
congenital heart disease
Pedigree
Phenotype
Sequence Analysis
medicine.medical_specialty
Genotype
Clinical Sciences
Polymorphism
Single Nucleotide
Article
tetralogy of fallot
03 medical and health sciences
Vasculogenesis
Internal medicine
Genetics
Humans
Genetic Predisposition to Disease
Polymorphism
Gene
Genetic Association Studies
Chromosomal Deletion
business.industry
Endothelial Cells
Chromosome
Sequence Analysis
DNA
DNA
medicine.disease
Neuropilin-1
030104 developmental biology
Endocrinology
business
Biomarkers
030217 neurology & neurosurgery
Zdroj: American journal of medical genetics. Part A, vol 176, iss 3
Duran, Ivan; Tenney, Jessica; Warren, Carmen M; Sarukhanov, Anna; Csukasi, Fabiana; Skalansky, Mark; et al.(2018). NRP1 haploinsufficiency predisposes to the development of Tetralogy of Fallot. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 176(3), 649-656. doi: 10.1002/ajmg.a.38600. UC Office of the President: Research Grants Program Office (RGPO). Retrieved from: http://www.escholarship.org/uc/item/1kz8q700
Am J Med Genet A
ISSN: 1552-4825
Popis: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. It involves anatomical abnormalities that change the normal flow of blood through the heart resulting in low oxygenation. Although not all of the underlying causes of TOF are completely understood, the disease has been associated with varying genetic etiologies including chromosomal abnormalities and Mendelian disorders, but can also occur as an isolated defect. In this report, we describe a familial case of TOF associated with a 1.8 Mb deletion of chromosome 10p11. Among the three genes in the region one is Neuropilin1 (NRP1), a membrane co-receptor of VEGF that modulates vasculogenesis. Hemizygous levels of NRP1 resulted in a reduced expression at the transcriptional and protein levels in patient-derived cells. Reduction of NRP1 also lead to decreased function of its activity as a co-receptor in intermolecular VEGF signaling. These findings support that diminished levels of NRP1 contribute to the development of TOF, likely through its function in mediating VEGF signal and vasculogenesis.
Databáze: OpenAIRE
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