Abstract
Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord. Three different forms of childhood SMA have been recognized on the basts of age at onset and clinical course: Werdnig-Hoffmann disease (type l), the intermediate form (type II) and Kugelberg-Welander disease (type III)1. A gene termed ‘survival of motor neuron’ (SMN) has been recognized as the disease-causing gene in SMA2–6. SMN encodes a protein located within a novel nuclear structure and interacts with RNA-binding proteins7. To elucidate the molecular mechanism underlying the pathogenesis of the disease, we examined the expression of the SMN gene in both controls and SMA patients by western blot and immunohistochemical analyses using antibodies raised against the SMN protein. The present study shows a marked deficiency of the SMN protein in SMA.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Munsat, T.L. Workshop report: international SMA collaboration. Neuromusc. Disord. 1, 81 (1991).
Lefebvre, S. et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80, 155–165 (1995).
Bussaglia, E. et al. A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. Nature Genet. 11, 335–337 (1995).
Rodrigues, N.R. et al. Deletions in the survival motor neuron gene on 5q13 in autosomal recessive spinal muscular atrophy. Hum. Mol. Genet. 4, 631–634 (1995).
Van der Steege, G. et al. PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet 345, 985–986 (1995).
Chang, J.G. et al. Molecular analysis of spinal muscular atrophy in Chinese. Am. J. Hum. Genet. 57, 1503–1505 (1995).
Liu, Q. & Dreyfuss, G. A novel nuclear structure containing the survival of motor neurons protein. EMBO J. 15, 3555–3565 (1996).
Roy, N. et al. The gene for neuronal apoptosis inhibitory protein (NAIP), a novel protein with homology to baculoviral inhibitors of apoptosis is partially deleted in individuals with type 1, 2 and 3 spinal muscular atrophy (SMA). Cell 80, 167–178 (1995).
Bürglen, L. et al. The gene encoding p44, a subunit of the transcription factor TFIIH, is involved in large-scale deletions associated with Werdnig-Hoffmann disease. Am. J. Hum. Genet. 60, 72–79 (1997).
Bignami, A., Eng, L.F., Dahl, D., & Uyeda, C.T. Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res. 43, 429–435 (1972).
Powers, M.M. & Clark, G. An evaluation of cresyl echt violet acetate as a Nissl stain. Stain Technol. 30, 83–88 (1955).
Andrade, L.E.C. et al. Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin. J. Exp. Med. 173, 1407–1419 (1991).
Dubowitz, V. Infantile spinal muscular atrophy: a prospective study with particular reference to a slowly progressive variety. Brain 87, 707–718 (1964).
Hahnen, E. et al. Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals. Hum. Mol. Genet. 4, 1927–1933 (1995).
Cobben, J.M. et al. Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy. Am. J. Hum. Genet. 57, 805–808 (1995).
Laemmli, U.K. Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227, 680–685 (1970).
Towbin, H, Staehelin, T. & Gordon, J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA 76, 4350–4354 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lefebvre, S., Burlet, P., Liu, Q. et al. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16, 265–269 (1997). https://doi.org/10.1038/ng0797-265
Issue Date:
DOI: https://doi.org/10.1038/ng0797-265
This article is cited by
-
Risdiplam improves subjective swallowing quality in non-ambulatory adult patients with 5q-spinal muscular atrophy despite advanced motor impairment
Journal of Neurology (2024)
-
Objective measurement of oral function in adults with spinal muscular atrophy
Orphanet Journal of Rare Diseases (2023)
-
Boosting neuregulin 1 type-III expression hastens SMA motor axon maturation
Acta Neuropathologica Communications (2023)
-
Long-term nusinersen treatment across a wide spectrum of spinal muscular atrophy severity: a real-world experience
Orphanet Journal of Rare Diseases (2023)
-
Prevalence of morbidities across the lifespan for adults with spinal muscular atrophy: a retrospective cohort study
Orphanet Journal of Rare Diseases (2023)