Could a DJ-1/PARK7 pathogenic variant be a cause of cardiac hypertrophy?—a case report

DJ-1, a protein encoded by the PARK7 gene, is crucial in the regulation of oxidative stress and mitochondrial function. Experimental studies in murine models suggest that DJ-1 deficiency results in pronounced cardiac hypertrophy and an elevated risk of heart failure, especially under conditions of oxidative stress. Nonetheless, this association had not yet been substantiated in human studies.

A 37-year-old male with early-onset Parkinson's disease due to a pathogenic variant of PARK7 presented with chest pain. Initial examination showed voltage criteria for left ventricular hypertrophy on ECG and concentric hypertrophy of the left ventricle on transthoracic echocardiography. Genetic testing confirmed a homozygous DJ-1 mutation. Other potential causes of concentric left ventricular hypertrophy, such as cardiac amyloidosis, Fabry disease, and sarcoidosis, were ruled out, leading to a final diagnosis of hypertrophic cardiomyopathy (HCM). A genetic analysis conducted to identify mutations in genes associated with HCM yielded negative results, supporting the conclusion that the patient’s cardiac hypertrophy may be linked to the pathogenic variant of PARK7.

To the best of our knowledge, this case represents the first documented instance in humans where the loss of DJ-1 protein has been implicated as a probable aetiology of HCM.