NASHVILLE, Tennessee—The level of expression of the MTCH2 gene may be involved in the timing and severity of cardiomyopathy in patients with Duchenne muscular dystrophy (DMD), according to a new study presented at the 2022 Muscular Dystrophy Association Clinical & Scientific Conference.

This might explain why some patients with DMD have severe cardiomyopathy while others have milder cardiomyopathy even though they all lack dystrophin protein. 

Elizabeth McNally, MD, professor of medicine (cardiology), biochemistry, and molecular genetics and the director of the Center for Genetic Medicine at the Northwestern University Feinberg School of Medicine in Chicago, Illinois, and her team identified the MTCH2 gene as having increased or deviant allele frequency in DMD patients with cardiomyopathy compared to those without.

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The MTCH2 gene codes for an outer mitochondrial membrane protein. Genome-wide association studies have shown that MTCH2 is associated with body mass index and obesity. 

Dr. McNally and her team were able to associate variants that increase the expression of MTCH2 with increased obesity and those that correlate with reduced expression with reduced obesity.

“The overall hypothesis is that reduced MTCH2 expression is associated with more lean body mass and increased MTCH2 expression is associated with obesity,” McNally said, adding that the finding was supported by mice experiments in which knocking out MTCH2 expression in skeletal and cardiac muscles protected the animals from diet-induced obesity. However, she added “too much loss of MTCH2” is also detrimental to the heart.

Read more about cardiomyopathy and other complications in DMD

Dr. McNally also presented some work conducted in her laboratory using a Drosophila model in which knocking down MTCH2 specifically in the heart reduced the movement of the heart tube of the flies. “This is because these hearts get a profound dilated cardiomyopathy,” she said. She added that reducing MTCH2 expression in the heart leads to reduced adiposity in the flies just like in humans.

When they metabolically analyzed the flies in which the MTCH2 was knocked down, the team found that lactate levels were increased while pyruvate levels were reduced.

“This is bad for the heart because a normal heart relies on using fatty acids as its primary fuel source,” Dr. McNally said. “As the heart begins to fail . . . it becomes highly dependent on glucose as its source of fuel.”

She concluded that for patients with DMD, the risk of developing cardiomyopathy is influenced by a combination of polygenic factors plus lifestyle.


McNally E. Genetics of cardiomyopathies in neuromuscular disorders. Oral presentation at: 2022 Muscular Dystrophy Association Clinical & Scientific Conference; March 14, 2022; Nashville, TN.