Truncating variant in myof gene is associated with limb-girdle type muscular dystrophy and cardiomyopathy

Artem Kiselev, Raquel Vaz, Anastasia Knyazeva, Alexey Sergushichev, Renata Dmitrieva, Aleksandr Khudiakov, John Jorholt, Natalia Smolina, Ksenia Sukhareva, Yulia Fomicheva, Evgeny Mikhaylov, Lubov Mitrofanova, Alexander Predeus, Gunnar Sjoberg, Dmitriy Rudenko, Thomas Sejersen, Anna Lindstrand, Anna Kostareva

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Article number608
JournalFrontiers in Genetics
Issue numberJUN
StatePublished - 2019


  • Cardiomyopathy
  • Haploinsufficiency
  • Muscular dystrophy
  • Myoferlin
  • Zebrafish


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