Brain, Vol. 124, No. 5, 907-915,
May 2001
© 2001 Oxford University Press
Mutations in the 5' region of the myotubularin-related protein 2 (MTMR2) gene in autosomal recessive hereditary neuropathy with focally folded myelin
1 University Department of Clinical Neurology and 2 Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK
Correspondence to:
Professor P. K. Thomas, University Department of Clinical Neurology, Institute of Neurology, Queen Square, London WC1N 3BG, UK E-mail: pkthotline{at}virgin.net
Focally folded myelin has been recognized as a distinctive feature in some individuals with severe inherited demyelinating neuropathy, with an onset in childhood. Such cases have been shown to be genetically heterogeneous. Alterations in the myotubularin-related protein 2 (MTMR2) gene on chromosome 11q22 have recently been shown to give rise to this phenotype. Mutations have been identified in the 3' region of the MTMR2 gene in four unrelated families, in two of whom the disorder had been mapped to chromosome 11q22 by genetic linkage analysis. We have sequenced the entire coding region and flanking intronic regions of the MTMR2 gene in eight families with early onset autosomal recessive neuropathies. Two novel mutations were identified in exon 4 at the 5' end of the MTMR2 gene in an English and an Indian family. The clinical phenotype and sural nerve pathology in these two families differs in severity, with the proband in the English family having an earlier onset and more severe neuropathy with prominent cranial nerve involvement. This is probably due to mutation type and possible involvement of small nucleotide polymorphisms in phenotype modulation. Detailed sural nerve pathology is presented in both cases. Mutations in the MTMR2 gene are thus an important cause of autosomal recessive demyelinating neuropathy. Identifying further mutations and defining their phenotype will help to clarify the genetic classification of this group of disorders.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Houlden, S. Hammans, H. Katifi, and M. M. Reilly A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H Neurology, February 17, 2009; 72(7): 617 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-M. Gaboreanu, R. Hrstka, W. Xu, M. Shy, J. Kamholz, J. Lilien, and J. Balsamo Myelin protein zero/P0 phosphorylation and function require an adaptor protein linking it to RACK1 and PKC{alpha} J. Cell Biol., May 21, 2007; 177(4): 707 - 716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bonneick, M. Boentert, P. Berger, S. Atanasoski, N. Mantei, C. Wessig, K. V. Toyka, P. Young, and U. Suter An animal model for Charcot-Marie-Tooth disease type 4B1 Hum. Mol. Genet., December 1, 2005; 14(23): 3685 - 3695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bolino, A. Bolis, S. C. Previtali, G. Dina, S. Bussini, G. Dati, S. Amadio, U. Del Carro, D. D. Mruk, M. L. Feltri, et al. Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis J. Cell Biol., November 22, 2004; 167(4): 711 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Berger, C. Schaffitzel, I. Berger, N. Ban, and U. Suter Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module PNAS, October 14, 2003; 100(21): 12177 - 12182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Previtali, B. Zerega, D. L. Sherman, P. J. Brophy, G. Dina, R. H.M. King, M. M. Salih, L. Feltri, A. Quattrini, R. Ravazzolo, et al. Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve Hum. Mol. Genet., July 15, 2003; 12(14): 1713 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-A Kim, P. O. Vacratsis, R. Firestein, M. L. Cleary, and J. E. Dixon Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase PNAS, April 15, 2003; 100(8): 4492 - 4497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Berger, S. Bonneick, S. Willi, M. Wymann, and U. Suter Loss of phosphatase activity in myotubularin-related protein 2 is associated with Charcot-Marie-Tooth disease type 4B1 Hum. Mol. Genet., June 15, 2002; 11(13): 1569 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-A Kim, G. S. Taylor, K. M. Torgersen, and J. E. Dixon Myotubularin and MTMR2, Phosphatidylinositol 3-Phosphatases Mutated in Myotubular Myopathy and Type 4B Charcot-Marie-Tooth Disease J. Biol. Chem., February 1, 2002; 277(6): 4526 - 4531. [Abstract] [Full Text] [PDF]
|
|