title: Clinical phenotype, muscle MRI and muscle pathology of LGMD1F.
abstract: Of the seven autosomal dominant genetically distinct forms of LGMD so far described, in only four the causative gene has been identified (LGMD1A-1D). We describe clinical, histopathological and muscle MRI features of a large Italo-Spanish kindred with LGMD1F presenting proximal-limb and axial muscle weakness. We obtained complete clinical data and graded the progression of the disease in 29 patients. Muscle MRI was performed in seven patients. Three muscle biopsies from two patients were investigated. Patients with age at onset in the early teens, had a more severe phenotype with a rapid disease course; adult onset patients presented a slow course. Muscle MRI showed prominent atrophy of lower limb muscles, involving especially the vastus lateralis. Widening the patients population resulted in the identification of previously unreported features, including dysphagia, arachnodactyly and respiratory insufficiency. Muscle biopsies showed diffuse fibre atrophy, which evolved with time, chronic myopathic changes, basophilic cytoplasmic areas, autophagosomes and accumulation of myofibrillar and cytoskeletal proteins. The LGMD1F is characterized by a selective involvement of limb muscles with respiratory impairment in advanced stages, and by different degrees of clinical progression. Novel clinical features emerged from the investigation of additional patients.
authors: Department of Neurosciences, University of Padova, Biomedical Campus "Pietro d'Abano", via Giuseppe Orus 2B, 35129 Padova, Italy.
authors: Enrico
authors: E
authors: Peterle
authors: Marina
authors: M
authors: Fanin
authors: Claudio
authors: C
authors: Semplicini
authors: Juan Jesus Vilchez
authors: JJ
authors: Padilla
authors: Vincenzo
authors: V
authors: Nigro
authors: Corrado
authors: C
authors: Angelini
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000502:physiology; D001706:Biopsy; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009460:Neurologic Examination; D010641:Phenotype; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases
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