AUTHOR=Kiselev Artem , Vaz Raquel , Knyazeva Anastasia , Sergushichev Alexey , Dmitrieva Renata , Khudiakov Aleksandr , Jorholt John , Smolina Natalia , Sukhareva Ksenia , Fomicheva Yulia , Mikhaylov Evgeny , Mitrofanova Lubov , Predeus Alexander , Sjoberg Gunnar , Rudenko Dmitriy , Sejersen Thomas , Lindstrand Anna , Kostareva Anna TITLE=Truncating Variant in Myof Gene Is Associated With Limb-Girdle Type Muscular Dystrophy and Cardiomyopathy JOURNAL=Frontiers in Genetics VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00608 DOI=10.3389/fgene.2019.00608 ISSN=1664-8021 ABSTRACT=

Even though genetic studies of individuals with neuromuscular diseases have uncovered the molecular background of many cardiac disorders such as cardiomyopathies and inherited arrhythmic syndromes, the genetic cause of a proportion of cardiomyopathies associated with neuromuscular phenotype still remains unknown. Here, we present an individual with a combination of cardiomyopathy and limb-girdle type muscular dystrophy where whole exome sequencing identified myoferlin (MYOF)—a member of the Ferlin protein family and close homolog of DYSF—as the most likely candidate gene. The disease-causative role of the identified variant c.[2576delG; 2575G>C], p.G859QfsTer8 is supported by functional studies in vitro using the primary patient’s skeletal muscle mesenchymal progenitor cells, including both RNA sequencing and morphological studies, as well as recapitulating the muscle phenotype in vivo in zebrafish. We provide the first evidence supporting a role of MYOF in human muscle disease.