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PMID: 15852399 Published · ppublish English Case Reports Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Distal spinal and bulbar muscular atrophy caused by dynactin mutation.

Annals of neurology ·Vol. 57 ·No. 5 ·2005-05-00 ·Pages 687-94

Puls I, Oh SJ, Sumner CJ, Wallace KE, Floeter MK, Mann EA, Kennedy WR, Wendelschafer-Crabb G, Vortmeyer A, Powers R, Finnegan K, Holzbaur EL, Fischbeck KH, Ludlow CL

Abstract

Impaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150Glued subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles. They later experienced weakness and atrophy in the face, hands, and distal legs. The extremity involvement was greater in the hands than in the legs, and it had a particular predilection for the thenar muscles. No clinical or electrophysiological sensory abnormality existed; however, skin biopsy results showed morphological abnormalities of epidermal nerve fibers. An autopsy study of one patient showed motor neuron degeneration and axonal loss in the ventral horn of the spinal cord and hypoglossal nucleus of the medulla. Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a unique pattern of motor neuron degeneration that is associated with the accumulation of dynein and dynactin in neuronal inclusions.

MeSH Terms
Action Potentials/physiology Adult Brain/pathology Dynactin Complex Electromyography Electrophysiology Female Humans Immunohistochemistry Laryngeal Diseases/etiology,pathology Male Microtubule-Associated Proteins/genetics Middle Aged Muscular Disorders, Atrophic/genetics,pathology Mutation, Missense/physiology Nerve Degeneration/pathology Nerve Fibers/pathology Neural Conduction/physiology Pedigree Peripheral Nerves/physiopathology Skin/innervation,pathology Spinal Cord/pathology Vocal Cord Paralysis/etiology,pathology Vocal Cords/pathology
Chemicals
Dynactin Complex Microtubule-Associated Proteins
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Puls Imke
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1416, USA.
Oh Shin J
Sumner Charlotte J
Wallace Karen E
Floeter Mary Kay
Mann Eric A
Kennedy William R
Wendelschafer-Crabb Gwen
Vortmeyer Alexander
Powers Richard
Finnegan Kimberly
Holzbaur Erika L F
Fischbeck Kenneth H
Ludlow Christy L
References (37)
37 references, click to expand
  1. CONGENITAL LARYNGEAL-ABDUCTOR PARALYSIS DUE TO NUCLEUS AMBIGUUS DYSGENESIS IN THREE BROTHERS.
    N Engl J Med. 1964 Sep 17;271:593-7 PMID: 14172969
  2. Distal spinal muscular atrophy with vocal cord paralysis (dSMA-VII) is not linked to the MPD2 locus on chromosome 5q31.
    J Med Genet. 2000 Aug;37(8):E14 PMID: 10922394
  3. Localization of the gene for distal hereditary motor neuronopathy VII (dHMN-VII) to chromosome 2q14.
    Am J Hum Genet. 2001 May;68(5):1270-6 PMID: 11294660
  4. Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21.
    Nat Genet. 2002 Jan;30(1):21-2 PMID: 11743579
  5. The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease.
    Nat Genet. 2002 Jan;30(1):22-5 PMID: 11743580
  6. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration.
    Neuron. 2002 May 30;34(5):715-27 PMID: 12062019
  7. Toxic proteins in neurodegenerative disease.
    Science. 2002 Jun 14;296(5575):1991-5 PMID: 12065827
  8. Mutant dynactin in motor neuron disease.
    Nat Genet. 2003 Apr;33(4):455-6 PMID: 12627231
  9. The gene for HMSN2C maps to 12q23-24: a region of neuromuscular disorders.
    Neurology. 2003 Apr 8;60(7):1151-6 PMID: 12682323
  10. Mutations in dynein link motor neuron degeneration to defects in retrograde transport.
    Science. 2003 May 2;300(5620):808-12 PMID: 12730604
  11. Retrograde transport redux.
    Neuron. 2003 Jul 3;39(1):1-2 PMID: 12848924
  12. Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene.
    Brain. 2003 Sep;126(Pt 9):2023-33 PMID: 12821518
  13. Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies.
    Neurology. 2003 Sep 9;61(5):631-6 PMID: 12963753
  14. Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila.
    Neuron. 2003 Sep 25;40(1):25-40 PMID: 14527431
  15. Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport.
    Neuron. 2003 Sep 25;40(1):41-52 PMID: 14527432
  16. A direct interaction between cytoplasmic dynein and kinesin I may coordinate motor activity.
    J Biol Chem. 2004 Apr 30;279(18):19201-8 PMID: 14985359
  17. Motor neurons rely on motor proteins.
    Trends Cell Biol. 2004 May;14(5):233-40 PMID: 15130579
  18. Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy.
    J Neurosci. 2004 May 12;24(19):4657-67 PMID: 15140937
  19. Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS.
    Neurology. 2004 Aug 24;63(4):724-6 PMID: 15326253
  20. Varying occurrence of vocal cord paralysis in a family with autosomal dominant hereditary motor and sensory neuropathy.
    J Neurol. 1999 Jul;246(7):552-5 PMID: 10463355
  21. Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons.
    Nat Neurosci. 1999 Jan;2(1):50-6 PMID: 10195180
  22. Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation.
    J Cell Biol. 1997 Dec 1;139(5):1307-15 PMID: 9382875
  23. Quantitation of epidermal nerves in diabetic neuropathy.
    Neurology. 1996 Oct;47(4):1042-8 PMID: 8857742
  24. Electrodes in laryngeal electromyography. Reliability comparison.
    Ann Otol Rhinol Laryngol. 1969 Feb;78(1):172-80 PMID: 5763185
  25. Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis.
    J Cell Biol. 1996 Feb;132(4):617-33 PMID: 8647893
  26. Electrophysiological study of diaphragmatic myoclonus.
    J Neurol Neurosurg Psychiatry. 1995 Apr;58(4):480-3 PMID: 7738561
  27. Hereditary motor and sensory neuropathy with diaphragm and vocal cord paresis.
    Ann Neurol. 1994 May;35(5):608-15 PMID: 8179305
  28. Distal spinal muscular atrophy with vocal cord paralysis.
    J Med Genet. 1992 Mar;29(3):197-9 PMID: 1552559
  29. Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ.
    Proc Natl Acad Sci U S A. 1983 Oct;80(19):6126-30 PMID: 6577472
  30. Hereditary distal spinal muscular atrophy with vocal cord paralysis.
    J Neurol Neurosurg Psychiatry. 1980 May;43(5):413-8 PMID: 7420092
  31. Bilateral abductor vocal cord paralysis in Charcot-Marie-Tooth disease.
    Ann Otol Rhinol Laryngol. 1979 Mar-Apr;88(2 Pt 1):205-9 PMID: 443714
  32. Autosomal dominantly inherited adductor laryngeal paralysis--a new syndrome with a suggestion of linkage to HLA.
    Clin Genet. 1978 Nov;14(5):265-70 PMID: 709905
  33. Hereditary abductor vocal cord paralysis.
    Ann Otol Rhinol Laryngol. 1976 Jan-Feb;85(1 Pt 1):90-3 PMID: 944010
  34. Familial laryngeal abductor paralysis and psychomotor retardation.
    Clin Genet. 1973;4(5):429-33 PMID: 4751313
  35. An electromyographic study of recurrent laryngeal nerve conduction and its clinical applications.
    Laryngoscope. 1973 May;83(5):796-807 PMID: 4702478
  36. The paralyzed larynx: an electromyographic study in dogs and humans.
    Laryngoscope. 1970 Oct;80(10):1455-517 PMID: 4921200
  37. Use of hooked-wire electrodes for electromyography of the intrinsic laryngeal muscles.
    J Speech Hear Res. 1969 Jun;12(2):362-73 PMID: 5808863
Article Info
Journal
Annals of neurology
Abbr.
Ann Neurol
ISSN
0364-5134
DOI
10.1002/ana.20468
Published
2005-05-00
Pages
687-94
Language
English
Region
United States
NLM ID
7707449
PMCID
PMC1351270
Subset
IM
Grants
NIGMS NIH HHS · R01 GM048661 · United States
Intramural NIH HHS · Z01 NS002980 · United States
NIGMS NIH HHS · GM48661 · United States
NINDS NIH HHS · Z01 NS02980 · United States
External Links
PubMed source DOI: 10.1002/ana.20468 PMC Full Text View journal details
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