New research has revealed how essential the FOCAD gene to maintain a healthy liver, especially in children. Children with loss-of-function mutations in FOCAD have been shown in a research study to have a pediatric form of early-onset liver cirrhosis that can be life-threatening. The research was developed by the scientists of the Genome Institute of Singapore (GIS) by A * STAR, in collaboration with hospitals and institutes in seven countries (India, United States, Saudi Arabia, Pakistan, Portugal, Brazil and France).
The results of the Research have been published in the scientific journal Nature Genetics.
FOCAD mutation: this is what it causes in children
Liver disease is becoming a major health concern and is estimated to be the fifth most common cause of death worldwide. A systematic review of the Global Burden of Disease Study identified 1.32 million deaths due to liver cirrhosis in 2017, accounting for more than two percent of total global deaths. There cirrhosis of the liver it is usually diagnosed in old age and is traditionally believed to be caused by environmental factors such as poor diet, viral hepatitis, or alcohol abuse.
In collaboration with physicians around the world, the team combined classic tools such as Mendelian genetics and animal models with modern technology such as deep sequencing and state-of-the-art gene editing tools to identify that the FOCAD gene is indispensable for maintaining health. of the liver in humans. Mutations in this gene cause an early-onset form of liver cirrhosis not previously documented. Findings from a single gene, or monogenic disorder, leading to childhood cirrhosis establish a strong genetic component for this liver disease, which was previously unknown.
In further study, the scientists revealed that FOCAD works as part of a molecular quality control mechanism that aids in translation, a fundamental cellular process by which proteins are made. The main cells of the liver, the hepatocytes, have been found to be highly dependent on this dynamic compared to other cell types. This is the first time that this translation-dependent quality control mechanism has been involved in liver health.
The team of experts also discovered one cytokine, CCL2, which is overproduced in patients with FOCAD deficiency and may play a key role in the progression of liver cirrhysis. Doctor Ricardo Moreno Traspas, a postdoctoral fellow of the Laboratory of Human and Therapeutic Genetics of GIS, and lead author of the study, explained: “FOCAD mutations lead to an overproduction of a number of proteins that may be key factors in disease progression. One example is the signaling mediator, CCL2, which attracts immune cells and promotes inflammation of the liver. Drugs that target this, or similar candidates, are potential therapeutic intervention points for cirrhotic patients. “
Professor Bruno ReversadeSenior Group Leader at GIS and corresponding author of the study, commented: “We report the clinical impact of recessive loss-of-function variants in the FOCAD gene and provide evidence of the importance of the surveillance pathway.mRNA SKI for hepatic homeostasis. The research also produces the first animal model of human disease, as well as in vitro biological systems that are now being used as platforms to identify and validate novel antifibrotic therapeutic targets ”.
Professor Patrick Tan, Executive Director of GIS, said: “The knowledge and tools generated in this study have the potential to aid in the development of innovative therapies for the most common forms of liver disease such as fatty liver and liver cancer. Our data from our clinic will also help doctors to identify new patients with this syndrome, to better understand the cellular and molecular mechanisms of the disease and, therefore, to provide a more accurate diagnosis, prognosis and treatment ”.
As regards the acute hepatitis detected in children in this period: “He has not been identified no link to the Covid-19 vaccine and a questionnaire administered to the cases, on food and personal habits, did not identify any common exposure ”, the ministry said. According to Medical Factsportal launched by the virologist Roberto Burionitoday under the scientific direction of Renata Gili: “At the present moment the cause is not known and this certainly constitutes a problem because we are faced with an entity unknown“.
“For each of us, there is nothing to do but keep calmdon’t worry and use the preventive measures that we already know and that reduce the transmission risk of many viral infections, such as a thorough hygiene of the hands and respiratory. There have been reports of sudden onset hepatitis in otherwise healthy children under the age of 10 ”. Then i numbers: “From January 2022 to today there have been 108 cases in the UK; in 8 a liver transplant was required. Some cases have also been reported in the USA, Denmark, the Netherlands, Ireland and Spain ”, the portal reads.
“It is uun ‘inflammation of the liver which recognizes different causes. The most common are viral, the so-called virus of hepatitis. In some cases “different viruses may be involved, or a autoimmune or toxic mechanism (for example some drugs). Often hepatitis heals without leaving any aftermath – it was explained in the portal – but sometimes it can become chronic and lead to dangerous consequences such as liver cirrhosis and cancer (let’s think, for example, of hepatitis B, for which fortunately we have a vaccine that is given to children) “.
“THE hepatitis viruses were excluded in all cases. Instead, they are studying other viral causes or environmental factors but it is – he specified Medical Facts – of hypotheses. The health authorities are investigating not to leave any unexplored but we must have patience and wait. In none of the cases in the UK had the children been vaccinated and this allows us, fortunately, to to exclude a link to the vaccine. The priority at the moment is rightly that of promptly identify the cause in order to better care for children and to implement any necessary public health measures a to prevent the onset of these hepatitis “.
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