Genetic Mutation Could Worsen Heart in Dystrophy Patients

Patients carrying a cystic fibrosis gene mutation may have a decline in heart function and could benefit from more aggressive and earlier cardiac interventions.

Cystic fibrosis gene mutation may accelerate heart function decline in patients with Duchenne muscular dystrophy (DMD), as per the new study by UT Southwestern researchers, published in the Journal of the American Heart Association.

The study could help doctors develop new strategies to preserve heart function in muscular dystrophy.

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DMD patients with missense mutation in CFTR gene have lower left ventricular ejection fraction, larger end-diastolic volume, and higher levels of N-terminal pro-B-type natriuretic peptide.
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DMD, caused by a mutation on the X chromosome, results in the failure to produce dystrophin, a protein that protects muscle cells from damage, which in turn causes progressive muscle weakness. The cause of death, before age 35 - is usually cardiomyopathy.

How cardiomyopathy manifests varies among patients considerably, explains Pradeep Mammen, M.D., associate professor in the department of internal medicine's division of cardiology at UTSW, who runs a cardiology clinic specifically for patients with DMD and other neuromuscular disorders.

Mammen and his colleagues suspected that the variability might result from an additional genetic variation, which may synergistically worsen heart function in DMD patients, accelerating the underlying cardiomyopathy.

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The team recruited 22 male patients with DMD from their clinic and 12 female carriers, mostly mothers of patients. Cardiac function was assessed in 32 of these volunteers using cardiac magnetic resonance imaging (cMRI), echocardiography, or cardiac computed tomography. Blood test was done to check for additional markers of cardiac function and to perform whole exome sequencing.

A single unit of the cystic fibrosis transmembrane regular (CFTR) gene known as a "missense" mutation, stood out due to its role in heart cells, which is responsible for creating channels in heart cells that let bicarbonate in and regulate cell electrolyte levels.

DMD patients with this missense mutation have lower left ventricular ejection fraction, larger end-diastolic volume, and higher levels of a protein named N-terminal pro-B-type natriuretic peptide.

Mammen says doctors who treat these patients might eventually test for this mutation to identify DMD patients who need more aggressive cardiac care at a younger age.

"Even with new strategies to treat these patients on the horizon, such as genome editing that could convert DMD to a less severe form known as Becker's muscular dystrophy, cardiomyopathy will continue to be a patient's most serious and life-ending consequence," says Mammen, who holds the Alfred W. Harris, M.D., Professorship in Cardiology.

"Finding ways to help preserve heart function over time could offer new hope for patients with DMD."

Source-Medindia