In a major scientific breakthrough, researchers at Mayo Clinic’s Center for Individualized Medicine have discovered a rare genetic mutation that can directly cause a common liver disease known as metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called nonalcoholic fatty liver disease.
This finding changes the long-standing belief that the condition is caused only by a mix of lifestyle and genetic factors. Instead, the study shows that in some people, a single inherited genetic change may be the main cause.
MASLD happens when fat builds up in the liver in people who drink little or no alcohol. Over time, this buildup can lead to inflammation and damage. In more serious cases, it can progress to scarring of the liver, known as fibrosis, and eventually to cirrhosis, which can cause liver failure or liver cancer.
Today, MASLD affects about one-third of adults worldwide, making it one of the most common liver diseases. Its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), is becoming a leading reason for liver transplants.
The newly discovered mutation was found in a gene called MET. This gene plays an important role in helping the liver repair itself and in controlling how the body processes fat. When the MET gene does not work correctly, fat can accumulate inside liver cells, leading to inflammation and long-term damage.
The research began with a puzzling case involving a woman and her father who both developed severe liver disease despite having none of the usual risk factors such as obesity, diabetes, or high cholesterol.
To find the cause, scientists analyzed more than 20,000 genes in their DNA. They discovered a tiny mutation in the MET gene that disrupted how the liver handled fat. This specific mutation had never been reported before in scientific records.
To confirm the results, the Mayo Clinic team worked with researchers at the Medical College of Wisconsin. Their experiments showed that the mutation interfered with the gene’s instructions, causing the liver to fail in processing fat properly. This demonstrated that a single genetic change could trigger the disease.
Researchers then examined a large genetic database from the Mayo Clinic’s Tapestry study, which includes DNA information from more than 100,000 people. Among nearly 4,000 adults with MASLD in this group, about 1 percent had rare changes in the same MET gene.
A portion of these mutations occurred in the exact same region as the one found in the original family, strongly supporting the gene’s role in causing liver disease.
Experts say this discovery opens new possibilities for personalized medicine. By identifying people who carry these rare mutations, doctors may one day be able to detect the disease earlier and develop treatments tailored to each person’s genetic profile. It also shows that rare genetic conditions can sometimes hide within common diseases, making them harder to recognize.
Mayo Clinic has been a leader in using genetic tools to solve complex medical problems. Its Program for Rare and Undiagnosed Diseases has helped thousands of patients by uncovering hidden causes of illness. Researchers believe that findings like this could lead to better ways to prevent and treat liver disease in the future.
Although more research is needed, this study provides a new understanding of MASLD and highlights how modern genetic science can reveal hidden causes of common health problems. It brings hope that personalized treatments may one day stop the disease before it becomes severe.
If you care about liver health, please read studies about simple habit that could give you a healthy liver, and common diabetes drug that may reverse liver inflammation.
For more information about health, please see recent studies about simple blood test that could detect your risk of fatty liver disease, and results showing this green diet may strongly lower non-alcoholic fatty liver disease.
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