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Autosomal dominant calpainopathy due to heterozygous CAPN3 C.643_663del21
Journal article   Peer reviewed

Autosomal dominant calpainopathy due to heterozygous CAPN3 C.643_663del21

Jennifer M Martinez‐Thompson, Zhiyv Niu, Jennifer A Tracy, Steven A Moore, Andrea Swenson, Eric D Wieben and Margherita Milone
Muscle & nerve, Vol.57(4), pp.679-683
04/2018
DOI: 10.1002/mus.25970
PMCID: PMC5915624
PMID: 28881388

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Abstract

ABSTRACT Introduction: A calpain‐3 (CAPN3) gene heterozygous deletion (c.643_663del21) was recently linked to autosomal dominant (AD) limb‐girdle muscular dystrophy. However, the possibility of digenic disease was raised. We describe 3 families with AD calpainopathy carrying this isolated mutation. Methods: Probands heterozygous for CAPN3 c.643_663del21 were identified by targeted next generation or whole exome sequencing. Clinical findings were collected for probands and families. Calpain‐3 muscle Western blots were performed in 3 unrelated individuals. Results: Probands reported variable weakness in their 40s or 50s, with myalgia, back pain, or hyperlordosis. Pelvic girdle muscles were affected with adductor and hamstring sparing. Creatine kinase was normal to 1,800 U/L, independent of weakness severity. Imaging demonstrated lumbar paraspinal muscle atrophy. Electromyographic findings and muscle biopsies were normal to mildly myopathic. Muscle calpain‐3 expression was reduced. Discussion: This study provides further evidence for AD calpainopathy associated with CAPN3 c.643_663del21. No pathogenic variants in other genes known to cause myopathy were detected. Muscle Nerve 57: 679–683, 2018
 autosomal dominant myopathy axial myopathy CAPN3 limb‐girdle muscular dystrophy

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