Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/6/1076 |
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| author | Mathieu Cerino Patricio González-Hormazábal Mario Abaji Sebastien Courrier Francesca Puppo Yves Mathieu Alejandra Trangulao Nicholas Earle Claudia Castiglioni Jorge Díaz Mario Campero Ricardo Hughes Carmen Vargas Rocío Cortés Karin Kleinsteuber Ignacio Acosta J. Andoni Urtizberea Nicolas Lévy Marc Bartoli Martin Krahn Lilian Jara Pablo Caviedes Svetlana Gorokhova Jorge A. Bevilacqua |
| author_facet | Mathieu Cerino Patricio González-Hormazábal Mario Abaji Sebastien Courrier Francesca Puppo Yves Mathieu Alejandra Trangulao Nicholas Earle Claudia Castiglioni Jorge Díaz Mario Campero Ricardo Hughes Carmen Vargas Rocío Cortés Karin Kleinsteuber Ignacio Acosta J. Andoni Urtizberea Nicolas Lévy Marc Bartoli Martin Krahn Lilian Jara Pablo Caviedes Svetlana Gorokhova Jorge A. Bevilacqua |
| author_sort | Mathieu Cerino |
| collection | DOAJ |
| description | 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 <i>DYSF</i> and <i>CAPN3</i>, accounting for 22% and 8.5% of the cases, respectively, followed by <i>DMD</i> (4.9%) and <i>RYR1</i> (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. |
| first_indexed | 2024-03-09T23:43:09Z |
| format | Article |
| id | doaj.art-b6d4a30088a545e0b6883988fde21b16 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T23:43:09Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-b6d4a30088a545e0b6883988fde21b162023-11-23T16:48:52ZengMDPI AGGenes2073-44252022-06-01136107610.3390/genes13061076Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean PopulationMathieu Cerino0Patricio González-Hormazábal1Mario Abaji2Sebastien Courrier3Francesca Puppo4Yves Mathieu5Alejandra Trangulao6Nicholas Earle7Claudia Castiglioni8Jorge Díaz9Mario Campero10Ricardo Hughes11Carmen Vargas12Rocío Cortés13Karin Kleinsteuber14Ignacio Acosta15J. Andoni Urtizberea16Nicolas Lévy17Marc Bartoli18Martin Krahn19Lilian Jara20Pablo Caviedes21Svetlana Gorokhova22Jorge A. Bevilacqua23Marseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FrancePrograma de Genética Humana, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380492, ChileMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FranceMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FranceMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FranceMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FrancePrograma de Genética Humana, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380492, ChileUnidad de Patología Neuromuscular, Departamento de Neurología y Neurocirugía, Clínica Dávila, Santiago 8431657, ChileUnidad de Neurología, Departamento de Pediatría, Clínica Las Condes, Santiago 7591047, ChileCentro de Imagenología, Hospital Clínico Universidad de Chile, Santiago 8380492, ChileUnidad Neuromuscular, Departamento Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago 8380492, ChileUnidad Neuromuscular, Departamento Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago 8380492, ChileNeurología Pediátrica Hospital Roberto del Río, Universidad de Chile, Santiago 8380492, ChileUnidad de Neurología, Departamento de Pediatría, Clínica Las Condes, Santiago 7591047, ChileUnidad de Neurología, Departamento de Pediatría, Clínica Las Condes, Santiago 7591047, ChileUnidad de Patología Neuromuscular, Departamento de Neurología y Neurocirugía, Clínica Dávila, Santiago 8431657, ChileInstitut de Myologie, Hôpital de la Pitié-Salpêtrière, 75013 Paris, FranceMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FranceMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FranceMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FrancePrograma de Genética Humana, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380492, ChilePrograma de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380492, ChileMarseille Medical Genetics Université, INSERM, U 1251, Aix-Marseille Université, 13005 Marseille, FranceUnidad Neuromuscular, Departamento Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago 8380492, ChileHereditary 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 <i>DYSF</i> and <i>CAPN3</i>, accounting for 22% and 8.5% of the cases, respectively, followed by <i>DMD</i> (4.9%) and <i>RYR1</i> (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.https://www.mdpi.com/2073-4425/13/6/1076limb-girdle muscle weaknessLGMDhereditary myopathieshigh-throughput sequencingnext-generation sequencingChile |
| spellingShingle | Mathieu Cerino Patricio González-Hormazábal Mario Abaji Sebastien Courrier Francesca Puppo Yves Mathieu Alejandra Trangulao Nicholas Earle Claudia Castiglioni Jorge Díaz Mario Campero Ricardo Hughes Carmen Vargas Rocío Cortés Karin Kleinsteuber Ignacio Acosta J. Andoni Urtizberea Nicolas Lévy Marc Bartoli Martin Krahn Lilian Jara Pablo Caviedes Svetlana Gorokhova Jorge A. Bevilacqua Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population Genes limb-girdle muscle weakness LGMD hereditary myopathies high-throughput sequencing next-generation sequencing Chile |
| title | Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population |
| title_full | Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population |
| title_fullStr | Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population |
| title_full_unstemmed | Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population |
| title_short | Genetic Profile of Patients with Limb-Girdle Muscle Weakness in the Chilean Population |
| title_sort | genetic profile of patients with limb girdle muscle weakness in the chilean population |
| topic | limb-girdle muscle weakness LGMD hereditary myopathies high-throughput sequencing next-generation sequencing Chile |
| url | https://www.mdpi.com/2073-4425/13/6/1076 |
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