Elucidation of the Genetic Cause in Dutch Limb Girdle Muscular Dystrophy Families: A 27-Year's Journey
| Autor: | L. ten Dam, Anneke J. van der Kooi, Ieke B. Ginjaar, Hermine A. van Duyvenvoorde, M. de Visser, Silvana van Koningsbruggen |
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| Přispěvatelé: | Neurology, ANS - Neuroinfection & -inflammation, Human Genetics, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, EURO-NMD |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Adolescent Ubiquitin-Protein Ligases Muscle Proteins Mitochondrial Membrane Transport Proteins Muscular Dystrophies whole exome sequencing Tripartite Motif Proteins SGCG symbols.namesake Limb girdle muscular dystrophy Young Adult gene panel Exome Sequencing medicine Sarcoglycanopathies Humans Genetic Testing Child sanger sequencing Cation Transport Proteins Dysferlin Exome sequencing Genetic testing SGCA Netherlands Genetics Sanger sequencing medicine.diagnostic_test business.industry Calpain Calcium-Binding Proteins Dystrophy High-Throughput Nucleotide Sequencing Sequence Analysis DNA Middle Aged medicine.disease Sarcoglycanopathy Phenotype Neurology Muscular Dystrophies Limb-Girdle Mutation symbols Female Neurology (clinical) business Limb-girdle muscular dystrophy Transcription Factors |
| Zdroj: | Journal of neuromuscular diseases, 8(2), 261-272. IOS Press JOURNAL OF NEUROMUSCULAR DISEASES JOURNAL OF NEUROMUSCULAR DISEASES, 8(2), 261-272. IOS PRESS |
| ISSN: | 2214-3602 2214-3599 |
| Popis: | Background: A Dutch cohort of 105 carefully selected limb girdle muscular dystrophy (LGMD) patients from 68 families has been subject to genetic testing over the last 20 years. After subsequent targeted gene analysis around two thirds (45/68) of the families had received a genetic diagnosis in 2013. Objective: To describe the results of further genetic testing in the remaining undiagnosed limb girdle muscular dystrophy families in this cohort. Methods: In the families of the cohort for whom no genetic diagnosis was established (n = 23) further testing using Sanger sequencing, next generation sequencing with gene panel analysis or whole-exome sequencing was performed. In one case DNA analysis for facioscapulohumeral dystrophy type 1 was carried out. Results: In eight families no additional genetic tests could be performed. In 12 of the remaining 15 families in which additional testing could be performed a genetic diagnosis was established: two LGMDR1 calpain3-related families with CAPN3 mutations, one LGMDR2 dysferlin-related family with DYSF mutations, three sarcoglycanopathy families (LGMDR3-5 α-, β- and γ-sarcoglycan-related) with SGCA/SGCB/SGCG mutations, one LGMDR8 TRIM 32-related family with TRIM32 mutations, two LGMDR19 GMPPB-related families with GMPPB mutations, one family with MICU1-related myopathy, one family with FLNC-related myopathy and one family with facioscapulohumeral dystrophy type 1. At this moment a genetic diagnosis has been made in 57 of the 60 families of which DNA was available (95%). Conclusion: A genetic diagnosis is obtained in 95% of the families of the original Dutch LGMD cohort of which DNA was available. |
| Databáze: | OpenAIRE |
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