Duchenne muscular dystrophy and early onset hypertrophic cardiomyopathy caused by co-occurring mutations in dystrophin and two hypertrophic cardiomyopathy-associated genes

Liam Aspit ^1,2 Aviva Levitas ³ Noga Arwas ³ Hanna Krymko ³ Yoram Etzion ^4,5 Ruti Parvari ^1,2

¹The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Israel
²The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Israel
³Department of Pediatric Cardiology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel
⁴Regenerative Medicine and Stem Cell Research Center and the Cardiac Research Laboratory, Ben-Gurion University of the Negev, Israel
⁵Department of Physiology and Cell Biology, Faculty of Health Sciences and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Israel

Duchenne muscular dystrophy (DMD) is a progressive muscular damage disorder caused by mutations in dystrophin. Cardiomyopathy may first be evident after 10 years of age and increases in incidence with age.

We present a male patient diagnosed at 18 months with a rare phenotype of Duchene in conjunction with early onset Hypertrophic cardiomyopathy (HCM). The cause of DMD is deletion of exons 51-54 of dystrophin. The cause for HCM was verified by whole exome sequencing. Novel missense variations in two genes: MAP2K5 inherited from the mother and ACTN2 inherited from the father, or de-novo. Their combination could be causing the HCM of the patient.

This is the second case of a patient diagnosed at relatively young age with Duchene and HCM, presenting novel variations in genes previously associated with HCM. This study demonstrates the need of genetic diagnosis for elucidating the underlying pathology of HCM.