AUTHOR=Massucco Sara , Fossa Paola , Fiorillo Chiara , Faedo Elena , Gemelli Chiara , Barresi Rita , Ripolone Michela , Patrone Serena , Gaudio Andrea , Mandich Paola , Gotta Fabio , Baratto Serena , Traverso Monica , Pisciotta Livia , Zaottini Federico , Camera Mattia , Scarsi Elena , Grandis Marina 

TITLE=Case report: A single novel calpain 3 gene variant associated with mild myopathy

JOURNAL=Frontiers in Genetics

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1437859

DOI=10.3389/fgene.2024.1437859

ISSN=1664-8021

ABSTRACT=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.