Mayo Clinic Uncovers Rare Gene Mutation Linked to Liver Disease

Researchers at the Mayo Clinic have identified a rare mutation in the MET gene that directly causes metabolic dysfunction-associated steatotic liver disease (MASLD), a condition previously linked primarily to lifestyle factors. This groundbreaking discovery, published on March 7, 2026, demonstrates that a single inherited genetic mutation can significantly influence the disease’s development.

The study originated from a case involving a father and daughter diagnosed with MASLD, despite lacking common risk factors such as diabetes or high cholesterol. This anomaly prompted an extensive genomic analysis, leading to the identification of a mutation that impairs the liver’s ability to process fat. Over time, this malfunction results in fat accumulation, potentially leading to inflammation, scarring, and even cirrhosis.

Understanding the Genetic Link

The findings highlight a shift in understanding the origins of MASLD. Previously, the condition was thought to arise from a combination of genetic predisposition and environmental influences. The research, led by Filippo Pinto e Vairo, M.D., Ph.D., medical director of the Program for Rare and Undiagnosed Diseases at the Mayo Clinic’s Center for Individualized Medicine, reveals that certain cases can be traced back to specific genetic alterations.

The mutation in the MET gene disrupts vital biological processes that manage fat metabolism in the liver. A single change in the DNA sequence affects how the liver processes fat, leading to the disease’s progression. This rare variant has not been previously documented in scientific literature or genetic databases, underscoring the uniqueness of this discovery.

“We are learning that rare inherited genetic variants can drive common diseases,” Dr. Pinto e Vairo stated. “This opens new avenues for understanding disease mechanisms and identifying potential therapeutic targets.”

Wider Implications and Future Research

To assess whether similar mutations exist in other patients, researchers turned to the Tapestry study, a large-scale exome sequencing initiative analyzing genetic factors influencing health. This project has gathered data from over 100,000 participants in the United States. Among nearly 4,000 adults with MASLD in the study, approximately 1% were found to carry rare variants in the MET gene, reinforcing the significance of this gene in liver disease.

Konstantinos Lazaridis, M.D., one of the lead authors, emphasized the potential impact of these findings. “This discovery could affect hundreds of thousands, if not millions, of people worldwide with or at risk for MASLD,” he remarked. The Tapestry study plays a crucial role in uncovering hidden genetic factors, contributing to a more nuanced understanding of complex disorders.

The Mayo Clinic researchers plan to conduct further studies to explore how these findings could inform the development of targeted treatments and improve diagnostic methods for MASLD. The implications of this work extend beyond individual cases, highlighting the importance of genomic medicine in unraveling the complexities of rare diseases.

The Program for Rare and Undiagnosed Diseases at Mayo Clinic has already provided comprehensive genomic testing to over 3,200 patients since its inception in 2019. Collaborating with nearly 300 clinicians from various divisions, the program aims to deliver precision diagnostics for hard-to-diagnose conditions, including rare liver diseases.

As genomic medicine continues to advance, the discovery of the MET gene mutation marks a significant step forward in understanding metabolic dysfunction-associated steatotic liver disease and bolstering efforts to develop effective treatments.