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

Mathieu Cerino (1) , Patricio Gonzalez-Hormazabal (2) , Mario Abaji (1) , Sebastien Courrier (1) , Francesca Puppo (1) , Yves Mathieu (1) , Alejandra Trangulao (2) , Nicholas Earle , Claudia Castiglioni , Jorge Diaz (3) , Mario Campero (3) , Ricardo Hughes (3) , Carmen Vargas (2) , Rocio Cortes (2) , Karin Kleinsteuber (2) , Ignacio Acosta , J. Andoni Urtizberea (4) , Nicolas Levy (1) , Marc Bartoli (1) , Martin Krahn (1, 5) , Lilian Jara (2) , Pablo Caviedes (2) , Svetlana Gorokhova (1) , Jorge A. Bevilacqua (3)

1 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
2 UCHILE - Universidad de Chile = University of Chile [Santiago]
3 Hospital Clínico Universidad de Chile
4 CHU Pitié-Salpêtrière [AP-HP]
5 Département de génétique médicale [Hôpital de la Timone - APHM]

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.

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

Domaines: Génétique

Mathieu Cerino, Patricio Gonzalez-Hormazabal, Mario Abaji, Sebastien Courrier, Francesca Puppo, et al.. Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population. Genes, 2022, 13 (6), ⟨10.3390/genes13061076⟩. ⟨hal-03780367⟩