South Australian researchers Discover responsible new gene mutations For causing stillbirth and severe chronic illness in affected children and providing new insights into lymphatic disease.
“We have discovered a genetic event that causes a rare lymphatic disease.” The study’s co-author, Professor Natasha Harvey, said.
The lymphatic system is a network of blood vessels and nodes that act as pipes and filters for interstitial fluid. Blood vessels and lymph nodes move adjacent to blood vessels, maintain fluid balance in tissues, but also transport immune cells to the site of infection in our body.
Central lymphatic abnormalities (CCLA), although rare, is a severe lymphatic disorder characterized by dilated lymph vessels, decreased lymphatic motility, and obstruction of blood vessels, resulting in inadequate fluid regurgitation.
“The effect of this disease is that fluid accumulates in the developing fetus. When fluid accumulates in the heart and lungs, it can cause respiratory problems and even death the fetus.”
Affected individuals often present with a variety of lymphatic conditions, including chylothorax (digestive lymph), pleural effusion (lung fluid), and chylothorax (chest fluid). All of these can die after chylothorax or chylothorax. birth.
The team researched to find out the underlying genetic reason for the disease 7 individuals affected by CCLA He discovered that six of them had mutations in two MDFIC genes.
Currently, there are few studies linking MDFIC to CCLA. CCLA was previously thought to be involved in the regulation of proteins involved in vascular tone and contractile vascular development. However, this study showed that individuals can cause CCLA if they carry two mutated MDFIC genes.
The team tested this by mutating the MDFIC gene on both chromosomes (homozygotes) of the mice and found that the mutated mice had difficulty breathing and all died shortly after birth.
The team found that mice shared the same pathology as humans affected by CCLA, and postmortem examinations showed that the lymphatic vessels in the mice were enlarged and abnormal lymphatic vessels and fluids into the digestive system. I found that it was accumulating. Both characteristics of human CCLA.
To investigate the role of MDFIC in mice, the authors studied mouse embryos, where the presence of MDFIC is not only important in the valves of blood vessels and lymph vessels, but also occurs in mutated mice, especially in the lymphatic system. I found that there are significantly fewer valves.
Valves are important in the lymphatic system And since they ensure the transport of fluid, intravenously. To maintain the unidirectional movement of the fluid, the valve closes as the fluid passes through it, preventing backflow.
A reduced or defective valve can affect the transport of liquid by allowing the liquid to flow back and accumulate in certain tissues and organs.
“If the lymph valves are not properly formed, lymph can accumulate in important organs such as the heart and lungs, causing major respiratory problems that can lead to childbirth and chronic illness,” the research team said. Professor Hamish Scott, who is in charge, said. ..
The authors investigated the role of MDFIC in the valves of human lymph cells and found that MDFIC regulates cell motility when mutated lymph cells become less motivated and valve development is inadequate. ..
“We have determined that MDFIC regulates cell migration, an important early event during lymphatic valve formation. The genetic variation found in our study is MDFIC in the lymphatic system. Reveals an important, previously unrecognized role in the disease, “says Scott.
Scott said their study emphasizes that “the development of one of the major parts of the lymphatic system, called the valve, is essential.”
By knowing the biochemical processes, he “has a much better idea of how to intervene therapeutically in the future for a broader group of diseases that affect the same system of the lymphatic system. You can get it. “
Finding the genetic cause of the disease “immediately affects the family in which the disease is inherited,” Harvey said.
Other gene mutations in CCLA Discovered in previous studiesThis is the first study to discover a causal relationship between the genes MDFIC and CCLA.
Few effective treatments are currently available, but by continually identifying the genetic cause of CCLA, Harvey says the next step is to develop new treatments to combat the disease. Said.
“There are existing medicines that can be used to treat these disorders, but we need to make sure that the signaling pathways treated by those medicines are the same pathways that affect our patients. “He said.
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Marina Chan is based in Melbourne and focuses on Australian news. Contact her at [email protected]