# Myopathy With Exercise‐Induced Intolerance due to Novel Biallelic Variants in OBSCN—A Clinical, Morphological and Molecular Analysis

## TL;DR

A new muscle disorder caused by OBSCN gene variants leads to exercise intolerance and is linked to disrupted calcium handling and cytoskeletal proteins.

## Contribution

Identifies two novel OBSCN variants and links them to dysregulated proteins affecting calcium and cytoskeletal integrity in skeletal muscle.

## Key findings

- OBSCN variants cause exercise intolerance with symptoms like myalgia and rhabdomyolysis.
- Proteomic analysis shows dysregulated proteins related to Ca2+ handling and cytoskeleton in affected muscle.
- Molecular findings highlight obscurin's critical role in skeletal muscle function and autophagy.

## Abstract

The phenotype of OBSCN variants consists of exercise intolerance ranging from myalgia and cramps to rhabdomyolysis. The symptoms are mainly induced by high‐intensity sports.Two previously undescribed OBSCN variants have been identified as being associated with exercise intolerance, myotonic discharges and core‐like lesions in the muscle biopsy.Proteomic analysis of skeletal muscle reveals that the pathogenicity of the OBSCN variants is associated with dysregulated proteins that control Ca2+ handling and the extrasarcomeric cytoskeleton.

The phenotype of OBSCN variants consists of exercise intolerance ranging from myalgia and cramps to rhabdomyolysis. The symptoms are mainly induced by high‐intensity sports.

Two previously undescribed OBSCN variants have been identified as being associated with exercise intolerance, myotonic discharges and core‐like lesions in the muscle biopsy.

Proteomic analysis of skeletal muscle reveals that the pathogenicity of the OBSCN variants is associated with dysregulated proteins that control Ca2+ handling and the extrasarcomeric cytoskeleton.

The phenotype of OBSCN variants consists of exercise intolerance ranging from myalgia and cramps to rhabdomyolysis. Symptoms are mainly induced by high‐intensity sports. Molecular analysis showing a deregulation of muscle processes associated with Ca2+ regulation, extrasarcolemmal integrity and autophagy emphasised the critical role of obscurin in skeletal muscle function.