Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population

Genes (Basel). 2022 Jun 16;13(6):1076. doi: 10.3390/genes13061076.

Abstract

Hereditary myopathies are a group of genetically determined muscle disorders comprising more than 300 entities. In Chile, there are no specific registries of the distinct forms of these myopathies. We now report the genetic findings of a series of Chilean patients presenting with limb-girdle muscle weakness of unknown etiology. Eighty-two patients were explored using high-throughput sequencing approaches with neuromuscular gene panels, establishing a definite genetic diagnosis in 49 patients (59.8%) and a highly probable genetic diagnosis in eight additional cases (9.8%). The most frequent causative genes identified were DYSF and CAPN3, accounting for 22% and 8.5% of the cases, respectively, followed by DMD (4.9%) and RYR1 (4.9%). The remaining 17 causative genes were present in one or two cases only. Twelve novel variants were identified. Five patients (6.1%) carried a variant of uncertain significance in genes partially matching the clinical phenotype. Twenty patients (24.4%) did not carry a pathogenic or likely pathogenic variant in the phenotypically related genes, including five patients (6.1%) presenting an autoimmune neuromuscular disorder. The relative frequency of the different forms of myopathy in Chile is like that of other series reported from different regions of the world with perhaps a relatively higher incidence of dysferlinopathy.

Keywords: Chile; LGMD; hereditary myopathies; high-throughput sequencing; limb-girdle muscle weakness; next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chile
  • Genetic Profile
  • Humans
  • Muscle Weakness / genetics
  • Muscular Diseases*
  • Muscular Dystrophies, Limb-Girdle* / epidemiology
  • Muscular Dystrophies, Limb-Girdle* / genetics

Grants and funding

This study was supported by grants from the Comisión Nacional de Investigación Científica y Tecnológica de Chile (FONDECYT 1151383 and Anillos ACT1121); the Vicerrectoría de Investigación y Desarrollo, Universidad de Chile (ENL15/14); Basal Centre, CeBiB, FB0001 and P09-022-F from ICM-ECONOMIA, Chile. The Corporación de Investigación de Neurología de Santiago (CINSAN) partially covered the article processing charges. The NGS analysis performed at DLE laboratories Rio de Janeiro, Brazil, was supported by Sanofi-Genzyme.