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CASE REPORT article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1437859

A Single Novel Calpain 3 Gene Variant Associated with Mild Myopathy

Provisionally accepted
Sara Massucco Sara Massucco 1*Paola Fossa Paola Fossa 2Chiara Fiorillo Chiara Fiorillo 3Elena Faedo Elena Faedo 1Chiara Gemelli Chiara Gemelli 4Rita Barresi Rita Barresi 5Michela Ripolone Michela Ripolone 6Serena Patrone Serena Patrone 1Andrea Gaudio Andrea Gaudio 4Paola Mandich Paola Mandich 1,4Fabio Gotta Fabio Gotta 4Serena Baratto Serena Baratto 7Monica Traverso Monica Traverso 8Livia Pisciotta Livia Pisciotta 4,9Federico Zaottini Federico Zaottini 4Mattia Camera Mattia Camera 1Elena Scarsi Elena Scarsi 1Marina Grandis Marina Grandis 1,4
  • 1 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy
  • 2 Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy
  • 3 Paediatric Neurology and Neuromuscular Disorders Unit, University of Genoa and IRCCS Istituto Giannina Gaslini, Genoa, Italy
  • 4 IRCCS Ospedale Policlinico San Martino, Genoa, Italy
  • 5 IRCCS San Camillo Hospital, Venice, Italy
  • 6 Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
  • 7 Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
  • 8 Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy
  • 9 Department of Internal Medicine (DiMI), School of Medical and Pharmaceutical Sciences, University of Genoa, Genoa, Italy

The final, formatted version of the article will be published soon.

    Recessively inherited limb-girdle muscular dystrophy type 1, caused by mutations in the calpain 3 gene, is the most common limb-girdle muscular dystrophy worldwide. Recently, cases of autosomal dominant calpainopathy have been described. A man was referred to our neurological outpatient clinic at the age of 54 for persistent hyperCKemia (>1000 U/l) associated with muscle fatigue and myalgia. Clinical examination revealed mild proximal weakness in the lower limbs. His brother exhibited a moderate increase in serum creatine kinase levels (up to 2000 U/l) without other signs of myopathy. Their father experienced slowly progressive lower limb weakness after the age of 50. The calpain 3 variant c.1478G>A (p.Arg493Gln) in the heterozygous state was identified in both brothers. In silico modeling studies predict that this substitution may disrupt protein folding. This represents the first description of the heterozygous p.Arg493Gln calpain 3 variant as a potential cause of mild calpainopathy.

    Keywords: Calpain, Calpainopathy, LGMD, LGMDR1, case report

    Received: 02 Jun 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Massucco, Fossa, Fiorillo, Faedo, Gemelli, Barresi, Ripolone, Patrone, Gaudio, Mandich, Gotta, Baratto, Traverso, Pisciotta, Zaottini, Camera, Scarsi and Grandis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Sara Massucco, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy

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