Related Experiment Video
Updated: May 2, 2026
07:36
Isolation of Human Lymphatic Endothelial Cells by Multi-parameter Fluorescence-activated Cell Sorting
Published on: May 1, 2015
13.8K
Genetics of lymphatic anomalies
The Journal of Clinical Investigation
|March 5, 2014
Summary
Genetic mutations in over 20 genes impact lymphatic vessel development, causing conditions like primary lymphedema. These genetic factors explain over a quarter of inherited lymphedema cases.
Area of Science:
- Vascular biology
- Human genetics
- Developmental biology
Background:
- Lymphatic anomalies encompass diverse defects of lymphatic vessels, including primary and secondary lymphedema, chylothorax, chylous ascites, lymphatic malformations, and overgrowth syndromes.
- Genetic factors are implicated in both sporadic and familial forms of these conditions.
Purpose of the Study:
- To investigate the genetic underpinnings of lymphatic anomalies.
- To identify genes and pathways involved in lymphatic vessel development and function.
Main Methods:
- Germline mutation analysis in patients with lymphatic anomalies.
- Identification of genes encoding proteins in VEGFR-3 signaling and other tyrosine kinase receptor pathways.
- Analysis of RAS/MAPK and PI3K/AKT signaling pathways.
Main Results:
- Mutations in at least 20 genes affecting VEGFR-3 signaling and downstream pathways were identified.
- These mutations account for over 25% of primary lymphedema cases, particularly inherited forms.
- Common forms may involve multigenic effects or post-zygotic mutations.
Conclusions:
- Germline mutations in specific genes are a significant cause of primary lymphedema and related lymphatic anomalies.
- The RAS/MAPK and PI3K/AKT pathways are crucial in the pathogenesis of these conditions.
- Differences in human and murine physiology may influence the manifestation of these genetic defects, as indicated by murine knockout studies.
Related Concept Videos
01:15Development of the Lymphatic System
2.8K
The development of lymphatic tissues and vessels in embryonic life begins around the fifth week. These structures originate from the mesoderm layer, with lymph sacs emerging from developing veins.
The first lymph sacs to form are the paired jugular lymph sacs located at the junction of the internal jugular and subclavian veins. From these sacs, lymphatic capillary plexuses extend to the thorax, upper limbs, neck, and head, eventually forming lymphatic vessels. Each jugular lymph sac maintains a...
The first lymph sacs to form are the paired jugular lymph sacs located at the junction of the internal jugular and subclavian veins. From these sacs, lymphatic capillary plexuses extend to the thorax, upper limbs, neck, and head, eventually forming lymphatic vessels. Each jugular lymph sac maintains a...
2.8K
01:16Lymphatic Vessels and Lymph Transport
13.6K
Lymphatic vessels, known as lymphatics, are crucial in transporting lymph from peripheral tissues to our venous system. This process begins with lymph entering through tiny capillaries that branch through tissues. These capillaries have unique features such as larger diameters, thinner walls, and a distinctive one-way valve system formed by overlapping endothelial cells.
This one-way system allows fluids, solutes, and even pathogens to enter but prevents their return to the intercellular...
This one-way system allows fluids, solutes, and even pathogens to enter but prevents their return to the intercellular...
13.6K
01:23Detailed Structure and Function of Lymph Nodes
13.4K
Lymph nodes are bean-shaped structures that cluster along the lymphatic vessels in the inguinal, axillary, and cervical regions. Each node is divided into compartments by a capsule that extends trabeculae inward.
From a histological perspective, lymph nodes can be split into two main areas: the superficial cortex and the deep medulla. The outer cortex is populated by dendritic cells, macrophages, and B lymphocytes, which are densely packed into follicles. When these B-lymphocytes are presented...
From a histological perspective, lymph nodes can be split into two main areas: the superficial cortex and the deep medulla. The outer cortex is populated by dendritic cells, macrophages, and B lymphocytes, which are densely packed into follicles. When these B-lymphocytes are presented...
13.4K
01:43Sex-linked Disorders
94.4K
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
94.4K
01:18Lymphoid Cells and Tissues
3.4K
Lymphoid cells and tissues are integral to the immune system, which is crucial in maintaining our body's defense against harmful pathogens. They form the building blocks of lymphoid organs, which include the spleen, thymus, and lymph nodes.
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...
Lymphoid cells consist of various types of immune system cells. These include B and T lymphocytes, which are responsible for producing antibodies and killing infected cells, respectively. Dendritic cells act as messengers between the innate and adaptive...
3.4K