The clinical spectrum of CASQ1-related myopathy

Claudio Semplicini, Cinzia Bertolin, Luca Bello, Boris Pantic, Francesca Guidolin, Sara Vianello, Francesco Catapano, Irene Colombo, Maurizio Moggio, Bruno F. Gavassini, Giovanna Cenacchi, Valentina Papa, Marco Previtero, Chiara Calore, Gianni Sorarù, Giovanni Minervini, Silvio C.E. Tosatto, Roberto Stramare, Elena Pegoraro

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: To identify and characterize patients with calsequestrin 1 (CASQ1)-related myopathy.

METHODS: Patients selected according to histopathologic features underwent CASQ1 genetic screening. CASQ1-mutated patients were clinically evaluated and underwent muscle MRI. Vacuole morphology and vacuolated fiber type were characterized.

RESULTS: Twenty-two CASQ1-mutated patients (12 families) were identified, 21 sharing the previously described founder mutation (p.Asp244Gly) and 1 with the p.Gly103Asp mutation. Patients usually presented in the sixth decade with exercise intolerance and myalgias and later developed mild to moderate, slowly progressive proximal weakness with quadriceps atrophy and scapular winging. Muscle MRI (n = 11) showed a recurrent fibrofatty substitution pattern. Three patients presented subclinical cardiac abnormalities. Muscle histopathology in patients with p.Asp244Gly showed vacuoles in type II fibers appearing empty in hematoxylin-eosin, Gomori, and nicotinamide adenine dinucleotide (NADH) tetrazolium reductase stains but strongly positive for sarcoplasmic reticulum proteins. The muscle histopathology of p.Gly103Asp mutation was different, showing also NADH-positive accumulation consistent with tubular aggregates.

CONCLUSIONS: We report the clinical and molecular details of the largest cohort of CASQ1-mutated patients. A possible heart involvement is presented, further expanding the phenotype of the disease. One mutation is common due to a founder effect, but other mutations are possible. Because of a paucity of symptoms, it is likely that CASQ1 mutations may remain undiagnosed if a muscle biopsy is not performed.

Original languageEnglish
Pages (from-to)e1629-e1641
Issue number17
Publication statusPublished - Oct 23 2018

ASJC Scopus subject areas

  • Clinical Neurology


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