Brain, Vol. 113, No. 5, 1511-1525, 1990
© 1990 Guarantors of Brain
research-article |
X-LINKED DOMINANT HEREDITARY MOTOR AND SENSORY NEUROPATHY
1Department of Clinical Neurological Sciences, University of Western Ontario, Victoria Hospital London, Ontario, Canada 2Department of Clinical Neurological Sciences, University of Western Ontario, University Hospital London, Ontario, Canada
Correspondence to:
Correspondence to: Dr. A. F. Hahn, Department of Neurological Sciences, Victoria Hospital, 373 South Street, London, Ontario N6A 4G5, Canada.
Modern techniques have defined the hereditary motor and sensory neuropathies (HMSN) as a genetically heterogenous group of disorders. This includes a rare variant with X-linked dominant inheritance. We have traced this disorder through 6 generations of a large Canadian kindred; neurological and electrophysiological examinations were performed in 57 family members and nerve biopsies were studied in 2 affected males, early and late in the disease; 42/83 family members were affected. No male-to-male transmission was encountered in 19 sons of affected fathers, whereas all their daughters expressed the disease. Linkage was shown to the DNA loci DXYS1 Z max = 2.87 at 
max = 0.06 and to PGK1 Z max = 1.51 at max = 0 (Beckett et al., 1986). The typical clinical features are onset in early childhood, pes cavus, atrophy and weakness of peroneal muscles and intrinsic hand muscles, and sensory abnormalities. Males were severely affected, whereas females had mild or subclinical disease. Electrophysiological observations indicated a substantial loss of distal motor and sensory nerve fibres. Evoked compound muscle action potentials in extensor digitorum brevis were absent or severely reduced in 42% of cases and the peroneal motor nerve conduction velocity was mildly reduced to a mean 36.5 ±7.4 m·s–1. Sural sensory nerve action potentials were absent or severely reduced in 75% of those affected. Nerve biopsies showed loss of myelinated and unmyelinated nerve fibres, regenerative sprouting and secondary demyelination. The findings indicate that this distinct variant of HMSN is the result of primary axonal degeneration.
Received August 22, 1989. Revised November 1, 1989. Accepted November 15, 1989.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E. Shy, C. Siskind, E. R. Swan, K. M. Krajewski, T. Doherty, D. R. Fuerst, P. J. Ainsworth, R. A. Lewis, S. S. Scherer, and A. F. Hahn CMT1X phenotypes represent loss of GJB1 gene function Neurology, March 13, 2007; 68(11): 849 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. G. Huttner, M. L. Kennerson, S. W. Reddel, D. Radovanovic, and G. A. Nicholson Proof of genetic heterogeneity in X-linked Charcot-Marie-Tooth disease Neurology, December 12, 2006; 67(11): 2016 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Dubourg, H. Azzedine, R. B. Yaou, J. Pouget, A. Barois, V. Meininger, D. Bouteiller, M. Ruberg, A. Brice, and E. LeGuern The G526R glycyl-tRNA synthetase gene mutation in distal hereditary motor neuropathy type V Neurology, June 13, 2006; 66(11): 1721 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Kleopa, E. Zamba-Papanicolaou, X. Alevra, P. Nicolaou, D. -M. Georgiou, A. Hadjisavvas, T. Kyriakides, and K. Christodoulou Phenotypic and cellular expression of two novel connexin32 mutations causing CMT1X Neurology, February 14, 2006; 66(3): 396 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Huang, E. E. Sirkowski, J. T. Stickney, and S. S. Scherer Prenylation-Defective Human Connexin32 Mutants Are Normally Localized and Function Equivalently to Wild-Type Connexin32 in Myelinating Schwann Cells J. Neurosci., August 3, 2005; 25(31): 7111 - 7120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Scherer, Y.-T. Xu, A. Messing, K. Willecke, K. H. Fischbeck, and L. J. B. Jeng Transgenic Expression of Human Connexin32 in Myelinating Schwann Cells Prevents Demyelination in Connexin32-Null Mice J. Neurosci., February 9, 2005; 25(6): 1550 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sevilla, A. Cuesta, M. J. Chumillas, F. Mayordomo, L. Pedrola, F. Palau, and J. J. Vilchez Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene Brain, September 1, 2003; 126(9): 2023 - 2033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hattori, M. Yamamoto, T. Yoshihara, H. Koike, M. Nakagawa, H. Yoshikawa, A. Ohnishi, K. Hayasaka, O. Onodera, M. Baba, et al. Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients Brain, January 1, 2003; 126(1): 134 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M-J Lee, I Nelson, H Houlden, M G Sweeney, D Hilton-Jones, J Blake, N W Wood, and M M Reilly Six novel connexin32 (GJB1) mutations in X-linked Charcot-Marie-Tooth disease J. Neurol. Neurosurg. Psychiatry, September 1, 2002; 73(3): 304 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Garbern, D. A. Yool, G. J. Moore, I. B. Wilds, M. W. Faulk, M. Klugmann, K.-A. Nave, E. A. Sistermans, M. S. van der Knaap, T. D. Bird, et al. Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation Brain, May 1, 2002; 125(3): 551 - 561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Dubourg, S. Tardieu, N. Birouk, R. Gouider, J. M. Leger, T. Maisonobe, A. Brice, P. Bouche, and E. LeGuern Clinical, electrophysiological and molecular genetic characteristics of 93 patients with X-linked Charcot-Marie-Tooth disease Brain, October 1, 2001; 124(10): 1958 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. H. FISCHBECK, A. ABEL, G. S. LIN, and S. S. SCHERER X-linked Charcot-Marie-Tooth Disease and Connexin32 Ann. N.Y. Acad. Sci., September 14, 1999; 883(1): 36 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. SCHERER Nodes, Paranodes, and Incisures: From Form to Function Ann. N.Y. Acad. Sci., September 14, 1999; 883(1): 131 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. LEWIS and A. J. SUMNER Electrophysiologic Features of Inherited Demyelinating Neuropathies: A Reappraisal Ann. N.Y. Acad. Sci., September 14, 1999; 883(1): 321 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. HAHN, C. F. BOLTON, C. M. WHITE, W. F. BROWN, S. E. TUUHA, C. C. TAN, and P. J. AINSWORTH Genotype/Phenotype Correlations in X-Linked Dominant Charcot-Marie-Tooth Disease Ann. N.Y. Acad. Sci., September 14, 1999; 883(1): 366 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. LEWIS and M. E. SHY Electrodiagnostic Findings in CMTX: A Disorder of the Schwann Cell and Peripheral Nerve Myelin Ann. N.Y. Acad. Sci., September 14, 1999; 883(1): 504 - 507. [Full Text] [PDF]
|
|
|
|
|
|
F L Mastaglia, K J Nowak, R Stell, B A Phillips, J E Edmondston, S M Dorosz, S D Wilton, J Hallmayer, B A Kakulas, and N G Laing Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy J. Neurol. Neurosurg. Psychiatry, August 1, 1999; 67(2): 174 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Castro, J. M. Gomez-Hernandez, K. Silander, and L. C. Barrio Altered Formation of Hemichannels and Gap Junction Channels Caused by C-Terminal Connexin-32 Mutations J. Neurosci., May 15, 1999; 19(10): 3752 - 3760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Bähr, F Andres, V Timmerman, M E Nelis, C Van Broeckhoven, and J Dichgans Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the connexin 32 gene J. Neurol. Neurosurg. Psychiatry, February 1, 1999; 66(2): 202 - 206. [Abstract] [Full Text]
|
|
|
|
|
|
S. S. Scherer, K. H. Fischbeck, N. Birouk, E. LeGuern, and P. Bouche Is CMTX an axonopathy? Neurology, January 1, 1999; 52(2): 432 - 432. [Full Text]
|
|
|
|
 |
|
 R. J. Balice-Gordon, L. J. Bone, and S. S. Scherer Functional Gap Junctions in the Schwann Cell Myelin Sheath J. Cell Biol., August 24, 1998; 142(4): 1095 - 1104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Bergoffen, S. Scherer, S Wang, M. Scott, L. Bone, D. Paul, K Chen, M. Lensch, P. Chance, and K. Fischbeck Connexin mutations in X-linked Charcot-Marie-Tooth disease Science, December 24, 1993; 262(5142): 2039 - 2042. [Abstract] [PDF]
|
|