The Genetic Mutation That Plagued Beethoven

Perhaps the greatest composer of all time, Beethoven had a simple but serious genetic mutation that affected the PNPLA3 protein – found in fat and liver cells. Out of 481 amino acids, he had a dangerous quirk: he had methionine at one important linkage instead of isoleucine. This meant the protein fumbled to do its job, breaking down fat in the liver, thereby causing levels of it to rise. And with fat, may have come fatty liver disease and a predisposition to liver scarring and cirrhosis.

Previous to this new Beethoven study, researchers had investigated the PNPLA3 mutation for links to fatty liver disease in all its forms, and in some cases, liver cancer. In 2008, a landmark study found fattier livers in people with the mutation, setting off a wave of other studies.