title: Clinical and pathological heterogeneity in late-onset partial merosin deficiency.
abstract: Mutations in the LAMA2 gene result in a complete loss of merosin and underlie a severe congenital type of muscular dystrophy (MDC1A).We investigated the clinical, genetic, and histological basis of late-onset muscular dystrophy in one family. The proband and her affected brother exhibited late-onset predominantly proximal muscle weakness. In addition, the proband experienced seizures. Magnetic resonance imaging of her brain demonstrated white-matter abnormalities. Sequencing of LAMA2 identified two new heterozygous point mutations in the two affected members. Muscle histology demonstrated dystrophic features, rimmed vacuoles, and partial loss of laminin α immunoreactivity. Partial merosin deficiency can present with a mild, late-onset limb-girdle-type pattern of weakness, with or without epilepsy, and pathologically may exhibit features observed in inclusion-body myopathy.
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Rajakulendran
authors.forename: Matt
authors.initials: M
authors.lastname: Parton
authors.forename: Janice L
authors.initials: JL
authors.lastname: Holton
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D004569:Electroencephalography / Q000379:methods; D005192:Family Health; D005260:Female; D006801:Humans; D007797:Laminin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000071456:Sequestosome-1 Protein; D049411:Utrophin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007797:Laminin; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D049411:Utrophin; C102645:laminin alpha 2