Two Novel Variants of the CAPN3 Gene in Chinese Patients with Limb-Girdle Muscular Dystrophy Recessive 1

Hum Hered. 2024;89(1):52-59. doi: 10.1159/000539521. Epub 2024 Jun 5.

Abstract

Introduction: Recessive mutations in the CAPN3 gene can lead to limb-girdle muscular dystrophy recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions.

Methods: We performed targeted next-generation sequencing of all exons of the CAPN3 gene in 4 patients with sporadic limb-girdle muscular dystrophy (LGMD) and further analyzed the effects of the novel identified variant using various software tools.

Results: We found 5 variants in CAPN3 gene in 4 patients, c.82_83insC (insertion mutation) and c.1115+2T>C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation.

Discussion: Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.

Keywords: CAPN3; Limb-girdle muscular dystrophy recessive 1; Muscle weakness; Novel mutations; Splice mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Calpain* / genetics
  • China
  • East Asian People / genetics
  • Exons / genetics
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Muscle Proteins* / genetics
  • Muscular Dystrophies, Limb-Girdle* / genetics
  • Mutation
  • Young Adult

Substances

  • Calpain
  • CAPN3 protein, human
  • Muscle Proteins

Supplementary concepts

  • Limb-girdle muscular dystrophy autosomal recessive