What does this research mean for the field?

Biallelic variants in OBSCN are linked to exercise-induced myopathy, myotonic discharges, and dysregulated calcium handling proteins in skeletal muscle. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to investigate the relationship between novel biallelic OBSCN variants and exercise-induced myopathy.

February 8, 2026Open Access

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

Key Result

Biallelic OBSCN variants cause exercise-induced myopathy with intolerance, myotonic discharges, core-like lesions, and altered Ca2+ handling proteins.

Key Points

This research aims to investigate the relationship between novel biallelic OBSCN variants and exercise-induced myopathy.
Clinical assessment of symptoms related to exercise intolerance.
Muscle biopsy for morphological analysis.
Proteomic analysis of skeletal muscle to identify protein dysregulation.
Identified two new OBSCN variants associated with exercise intolerance.
Symptoms include myalgia, cramps, and rhabdomyolysis during high-intensity exercise.
Muscle biopsy shows myotonic discharges and core-like lesions.
Proteomic analysis reveals dysregulation of proteins involved in calcium handling and cytoskeletal function.

Structured PICO

Population

Patients with exercise intolerance ranging from myalgia and cramps to rhabdomyolysis

Outcome

Identification of novel OBSCN variants and their pathophysiological mechanisms via clinical, morphological, and proteomic analysis

Novel biallelic variants in OBSCN cause a myopathy characterized by exercise intolerance, linked to dysregulated calcium handling and cytoskeletal proteins.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Summary 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 Ca 2+ handling and the extrasarcomeric cytoskeleton.