Genetic and phenotypic characteristics of 3 patients with limb-girdle muscular dystrophy: experience in a medical center in Mexico

Abstract Introduction Limb-girdle muscular dystrophy (LGMD) is a heterogeneous group of genetically inherited muscular disorders. Due to the inherent phenotypic variation among different LGMD forms, clinical diagnosis remains challenging. Guidelines recommend targeted sequencing based on the clinical characteristics of the disease. However, literature regarding the genotypic and phenotypic characterization of LGMD in Mexico is limited. We aimed to characterize a group of patients with an LGMD diagnosis at our center. Methods Patients exhibiting clinical features consistent with LGMD and a high probability of the condition based on the ALDA score were selected. Genomic DNA was extracted, and next-generation sequencing (NGS) was performed using a 10-gene panel. Detected variants were confirmed via Sanger sequencing and classified according to the American College of Medical Genetics and Genomics criteria. Results Twenty patients were included in the study. LGMD R2 DYSF-related was confirmed in two patients, while LGMD R1 CAPN3-related was confirmed in one patient. A novel pathogenic frameshift variant was detected in CAPN3. Two additional patients displayed an LGMD phenotype but could not be genetically confirmed: One was heterozygous for a variant of uncertain significance in DYSF, while the other was heterozygous for a pathogenic variant in DYSF. In the confirmed LGMD cases, the ALDA software accurately included the definitive diagnosis among its predictions. Conclusion We confirmed and characterized two cases of LGMD R2 DYSF-related and one case of LGMD R1 CAPN3-related among 20 patients with muscular dystrophy. Additionally, we identified a novel pathogenic frameshift variant in CAPN3. This study expands the genetic and phenotypic landscape of LGMD in Mexican patients.