Open Access

Compound heterozygous CAPN3 variants identified in a family with limb-girdle muscular dystrophy recessive 1

  • Authors:
    • Cheng Zhang
    • Xueping Zheng
    • Deguo Lu
    • Lulu Xu
    • Fengyuan Che
    • Shiguo Liu
  • View Affiliations

  • Published online on: April 23, 2021     https://doi.org/10.3892/mmr.2021.12119
  • Article Number: 480
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), a rare subtype of muscular dystrophy, is characterized by progressive muscle weakness and degeneration with a predominant presentation on the shoulder, pelvic and proximal limb muscles. Variants in calcium-activated neutral proteinase 3 (CAPN3), which encodes an enzyme, calpain 3, are considered the major cause of LGMDR1. The present study was conducted to identify the variants responsible for clinical symptoms in a Chinese patient with limb-girdle muscular dystrophies (LGMDs) and explore its genotype-phenotype associations. A series of clinical examinations were conducted, including blood tests and magnetic resonance imaging scans of the lower legs, electromyography and muscle biopsy on the proband diagnosed with muscular dystrophies. Genomic DNA was extracted from the peripheral blood of a three-person family with LGMDs and pathogenic variants detected by whole-exome sequencing (WES) were verified by Sanger sequencing. The WES of this patient revealed compound heterozygous variants in CAPN3, c.2120A>G/p.(Asp707Gly) in exon 20 and c.2201_2202delAT/p.(Tyr734*) in exon 21, which were inherited from his parents and absent from 200 control individuals of similar ethnic origin, indicating that these variants are the pathogenic triggers of the LGMDR1 phenotype. Notably, these CAPN3 sequence variants were related to LGMDR1 pathogenesis in this three-person family. The newly discovered c.2201_2202delAT/p.(Tyr734*) expands the current CAPN3 variant spectrum, improving the understanding of the conditions required to develop molecular diagnostic tools and for genetic counseling, particularly for families with a history of autosomal recessive LGMDs.
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June-2021
Volume 23 Issue 6

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Spandidos Publications style
Zhang C, Zheng X, Lu D, Xu L, Che F and Liu S: Compound heterozygous <em>CAPN3</em> variants identified in a family with limb-girdle muscular dystrophy recessive 1. Mol Med Rep 23: 480, 2021
APA
Zhang, C., Zheng, X., Lu, D., Xu, L., Che, F., & Liu, S. (2021). Compound heterozygous <em>CAPN3</em> variants identified in a family with limb-girdle muscular dystrophy recessive 1. Molecular Medicine Reports, 23, 480. https://doi.org/10.3892/mmr.2021.12119
MLA
Zhang, C., Zheng, X., Lu, D., Xu, L., Che, F., Liu, S."Compound heterozygous <em>CAPN3</em> variants identified in a family with limb-girdle muscular dystrophy recessive 1". Molecular Medicine Reports 23.6 (2021): 480.
Chicago
Zhang, C., Zheng, X., Lu, D., Xu, L., Che, F., Liu, S."Compound heterozygous <em>CAPN3</em> variants identified in a family with limb-girdle muscular dystrophy recessive 1". Molecular Medicine Reports 23, no. 6 (2021): 480. https://doi.org/10.3892/mmr.2021.12119