ABSTRACT
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 (nâ=â23) 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-, ß- 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.
Subject(s)
Muscular Dystrophies, Limb-Girdle/genetics , Adolescent , Adult , Calcium-Binding Proteins , Calpain , Cation Transport Proteins , Child , Dysferlin , Female , Genetic Testing , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mitochondrial Membrane Transport Proteins , Muscle Proteins , Muscular Dystrophies/genetics , Mutation , Netherlands , Phenotype , Sarcoglycanopathies/genetics , Sequence Analysis, DNA , Transcription Factors , Tripartite Motif Proteins , Ubiquitin-Protein Ligases , Exome Sequencing , Young AdultABSTRACT
In this review we discuss the use of conventional (computed tomography, magnetic resonance imaging, ultrasound) and advanced muscle imaging modalities (diffusion tensor imaging, magnetic resonance spectroscopy) in hereditary and acquired myopathies. We summarize the data on specific patterns of muscle involvement in the major categories of muscle disease and provide recommendations on how to use muscle imaging in this field of neuromuscular disorders.