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Novel Obscn Variants Associated With a Risk to Exercise-Intolerance and Rhabdomyolysis Publisher Pubmed



Zemorshidi F1, 2, 3 ; Topf A4 ; Claeys KG5, 6 ; Mcfarlane A4 ; Patton A4 ; Nafissi S1, 2 ; Straub V4
Authors
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Authors Affiliations
  1. 1. Neuromuscular Research Center, Tehran University of Medical Sciences, Iran
  2. 2. Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Neurology, Mashhad University of Medical Sciences, Mashhad, Iran
  4. 4. John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
  5. 5. Department of Neurology, University Hospitals Leuven, Leuven, Belgium
  6. 6. Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, and Leuven Brain Institute (LBI), Leuven, Belgium

Source: Neuromuscular Disorders Published:2024


Abstract

Obscurin, encoded by the OBSCN gene, is a muscle protein consisting of three main splice isoforms, obscurin-A, obscurin-B, and obscurin kinase-only protein (also known as KIAA1639 or Obsc-kin). Obscurin is located at the M-band and Z-disks and interacts with titin and myomesin. It plays an important role in the stability and maintenance of the A- and M-bands and the subsarcolemmal organization of the microtubule network. Furthermore, obscurin is involved in Ca2+ regulation and sarcoplasmic reticulum function and is connected to several other muscle proteins. OBSCN gene variants have been reported to be relatively common in inherited cardiomyopathies. Here we reported two young patients with a history of cramps, myalgia, exercise intolerance, rhabdomyolysis, and myoglobinuria without any evidence of concomitant cardiomyopathy in association with novel OBSCN variants (c.24822C>A and c.2653+1G>C). Obscurin-deficient muscle fibers seem to have increased susceptibility to damage triggered by exercise that may lead to rhabdomyolysis. More studies are needed to clarify the diverse clinical phenotypes and the pathophysiology of OBSCN gene variants. © 2023
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