A retrospective study on the clinical and molecular outcomes of calpainopathy in a Turkish patient cohort

Authors

İzem Olcay ŞAHİNFollow
Emine KARATAŞFollow
Mikail DEMİRFollow
Büşra TANFollow
Hüseyin PERFollow
Yusuf ÖZKULFollow
Munis DÜNDARFollow

DOI

10.55730/1300-0144.5769

Abstract

Calpainopathy, also known as limb-girdle muscular dystrophy recessive type 1, is a progressive muscle disorder that impacts the muscles around the hips and shoulders. The disease is caused by defects in the CAPN3 gene and can be inherited in both recessive and dominant forms. In this retrospective study, we aimed to evaluate the clinical and molecular results of our patients with calpainopathy and to examine the CAPN3 variants in Turkish and global populations.Materials and methods: Molecular analyses were performed using the next-generation sequencing (NGS) method. CAPN3 variants were identified through the examination of various databases.Results: In this retrospective study, the cohort consisted of seven patients exhibiting the CAPN3 (NM_000070.3) mutation and a phenotype compatible with calpainopathy at a single center in Türkiye. All patients displayed high CK levels and muscle weakness. We report a novel missense c.2437G>A variant that causes the autosomal dominant form of calpainopathy. Interestingly, the muscle biopsy report for the patient with the novel mutation indicated sarcoglycan deficiency. Molecular findings for the remaining individuals in the cohort included a compound heterozygous variant (frameshift and missense), one homozygous nonsense, one homozygous intronic deletion, and three homozygous missense variants. The most common variant in the Turkish population was c.550del. In both populations, pathogenic variants were most frequently located in exon 21, according to exon length. Variants were stochastically distributed based on consequences in CAPN3 domains.Conclusion: Therefore, the NGS method proves highly effective in diagnosing rare diseases characterized by clinical heterogeneity. Assessing variants based on ethnicity holds significance in the development of precise therapies.

Keywords

LGMDR1, LGMD2A, LGMDD1, NGS, variants

First Page

86

Last Page

98

Recommended Citation

ŞAHİN, İzem Olcay; KARATAŞ, Emine; DEMİR, Mikail; TAN, Büşra; PER, Hüseyin; ÖZKUL, Yusuf; and DÜNDAR, Munis (2024) "A retrospective study on the clinical and molecular outcomes of calpainopathy in a Turkish patient cohort," Turkish Journal of Medical Sciences: Vol. 54: No. 1, Article 11. https://doi.org/10.55730/1300-0144.5769
Available at: https://journals.tubitak.gov.tr/medical/vol54/iss1/11