title: The ultrastructure of peripheral nerve, motor end-plate and skeletal muscle in patients suffering from spinal muscular atrophy with respiratory distress type 1 (SMARD1).
abstract: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is genetically and clinically distinct from classic spinal muscular atrophy (SMA1). It results from mutations in the gene encoding immunoglobulin mu-binding protein 2 (IGHMBP2) on chromosome 11q13. Patients develop distally pronounced muscular weakness and early involvement of the diaphragm, resulting in respiratory failure. Sensory and autonomic nerves are also affected at later stages of the disease. We investigated peripheral nerves, skeletal muscles and neuromuscular junctions (NMJ) ultrastructurally in five unrelated patients and three siblings with genetically confirmed SMARD1. In mixed motor and sensory nerves we detected Wallerian degeneration and axonal atrophy similar to the ultrastructural findings described in SMA1. Isolated axonal atrophy was evident in purely sensory nerves. All investigated NMJ of patients with SMARD1 were dysmorphic and lacked a terminal axon. Moreover, we also observed characteristics of neuropathies, such as abnormalities in myelination, that have not been described in spinal muscular atrophies so far. Based on these findings we conclude that impairment of IGHMBP2 function leads to axonal degeneration, abnormal myelin formation, and motor end-plate degeneration.
authors: Department of Paediatric Neurology, Charité, Medical Faculty, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. alexander.diers@charite.de
authors: Alexander
authors: A
authors: Diers
authors: Marcel
authors: M
authors: Kaczinski
authors: Katja
authors: K
authors: Grohmann
authors: Christoph
authors: C
authors: Hübner
authors: Gisela
authors: G
authors: Stoltenburg-Didinger
mesh_terms: D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D046529:Microscopy, Electron, Transmission; D009046:Motor Neurons / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D009134:Muscular Atrophy, Spinal / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000473:pathology / Q000648:ultrastructure; D010525:Peripheral Nerves / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics; D014855:Wallerian Degeneration / Q000473:pathology / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors