A Case of a Patient with Calpainopathy Carrying Compound Heterozygous Mutations of a de novo Pathogenic Variant of c.1333G>A and a Novel Variant of c.1331C>T in CAPN3

Shogo Komaki; Akatsuki Kubota; Kazuto Katsuse; Asuka Kitamura; Meiko Maeda; Takashi Matsukawa; Nobuyuki Eura; Yoshihiko Saito; Ichizo Nishino; Tatsushi Toda

doi:10.2169/internalmedicine.3435-23

A Case of a Patient with Calpainopathy Carrying Compound Heterozygous Mutations of a de novo Pathogenic Variant of c.1333G>A and a Novel Variant of c.1331C>T in CAPN3

Intern Med. 2024 Mar 18. doi: 10.2169/internalmedicine.3435-23. Online ahead of print.

Authors

Affiliations

¹ Department of Neurology, The University of Tokyo, Japan.
² Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University School of Medicine, Japan.
³ Department of Neuromuscular Research, National Center of Neurology and Psychiatry, Japan.

PMID: 38494715
DOI: 10.2169/internalmedicine.3435-23

Abstract

Calpainopathy is primarily an autosomal recessive inherited myopathy; however, dominantly inherited cases with a pathogenic variant of c.1333G>A have been reported. A 13-year-old Japanese girl presented with toe walking and elevated serum creatine kinase levels. Genetic panel testing revealed compound heterozygosity for c.1333G>A and a novel variant of c.1331C>T in CAPN3, leading to a diagnosis of calpainopathy. A genetic analysis of her parents revealed the possibility that c.1333G>A was de novo. In this patient, the onset age was earlier than that of the reported autosomal dominant cases, suggesting the influence of the novel variant in the contralateral allele.

Keywords: CAPN3; Calpainopathy; LGMDR1; limb-girdle muscular dystrophy; toe walking.