Related Experiment Video

Updated: Aug 18, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.8K

A novel stop-gain pathogenic variant in FLT4 and a nonsynonymous pathogenic variant in PTPN11 associated with

Avisa Tabib1, Taravat Talebi2, Serwa Ghasemi3

  • 1Heart Valve Diseases Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

European Journal of Medical Research
|December 10, 2022
PubMed

Insights

This study identifies novel genetic variants in FLT4 and PTPN11 associated with congenital heart defects (CHDs). Whole-exome sequencing (WES) is a powerful tool for diagnosing CHDs with complex genetic causes.

Area of Science:

  • Genetics
  • Cardiology
  • Developmental Biology

Background:

  • Congenital heart defects (CHDs) are the most common birth malformations affecting the heart and great vessels.
  • CHD complications vary based on defect type, impacting outcomes like birth weight, prematurity, and mortality.

Purpose of the Study:

  • To investigate the genetic underpinnings of CHDs in unrelated families.
  • To identify novel gene variants associated with congenital heart defects.

Main Methods:

  • Whole-exome sequencing (WES) was employed on three unrelated pedigrees with CHDs.
  • Candidate variants were confirmed using PCR-based Sanger sequencing and bioinformatics analysis.

Main Results:

  • A novel stop-gain variant (c.C244T:p.R82X) in the FLT4 gene was identified.
  • A nonsynonymous variant (c.C1403T:p.T468M) in the PTPN11 gene was also detected.
  • FLT4, encoding vascular endothelial growth factor 3, is crucial for lymphatic development.

Conclusions:

  • This research is the first to report a novel FLT4 gene variant linked to CHDs.
  • A PTPN11 gene variant, encoding protein-tyrosine phosphatase, was identified.
  • Whole-exome sequencing (WES) shows clinical utility in diagnosing genetic variants in heterogeneous diseases like CHDs.
Abstract

Keywords:
CHDsCongenital heart defectFLT4PTPN11VEGFR3Whole-exome sequencing

More Related Videos

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

9.8K
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.1K

Related Concept Videos

Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
324
Pulmonary Hypertension: Classification and Pathogenesis01:30

Pulmonary Hypertension: Classification and Pathogenesis

Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
There are various classifications for PH, each relating to different underlying causes and also...
260
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
17.9K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
15.6K
Point and Frameshift Mutations01:30

Point and Frameshift Mutations

Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
56
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.4K