Skip Navigation



Brain Advance Access published online on June 4, 2003
Brain, doi:10.1093/brain/awg162
© 2003 by Guarantors of Brain
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
126/7/1545    most recent
awg162v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gommans, I. M. P.
Right arrow Articles by Kremer, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gommans, I. M. P.
Right arrow Articles by Kremer, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2003 The Guarantors of Brain

Article

A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions

I. M. P. Gommans 1*, M. Davis 2*, K. Saar 3*, M. Lammens 4, F. Mastaglia 5, P. Lamont 2, G. van Duijnhoven 6, H. J. ter Laak 4, A. Reis 3, O. J. M. Vogels 7, N. Laing 8, B. G. M. van Engelen 9*, and H. Kremer 10

1 Neuromuscular Center Nijmegen, Institute of Neurology, HB Nijmegen, The Netherlands; Department of Neurology, St Elisabeth Hospital, Tilburg, The Netherlands
2 Neurogenetic Unit, Departments of Neurology and Anatomical Pathology, Royal Perth Hospital, Perth, Australia
3 Max-Delbrück-Centre for Molecular Medicine, Berlin, Germany
4 Neuromuscular Center Nijmegen, Institute of Neurology, HB Nijmegen, The Netherlands; Department of Pathology, University Medical Center Nijmegen, HB Nijmegen, The Netherlands
5 Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, Western Australia, Australia
6 Department of Human Genetics, University Medical Center Nijmegen, HB Nijmegen, The Netherlands
7 Neuromuscular Center Nijmegen, Institute of Neurology, HB Nijmegen, The Netherlands; Department of Neurology, Antonius Hospital, Nieuwegein, The Netherlands
8 Neurogenetic Unit, Departments of Neurology and Anatomical Pathology, Royal Perth Hospital, Perth, Australia; Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Nedlands, Western Australia, Australia
9 Neuromuscular Center Nijmegen, Institute of Neurology, HB Nijmegen, The Netherlands
10 Department of Human Genetics, University Medical Center Nijmegen, HB Nijmegen, The Netherlands; Department of Otorhinolaryngology, University Medical Center Nijmegen, HB Nijmegen, The Netherlands

* Corresponding author. E-mail: b.g.m.vanengelmen{at}neuro.umcn.nl.

Received 12 November 2002 ; revised 28 February 2003 ; accepted 3 March 2003

Abstract

Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness and the presence of nemaline rods. Five genes have now been associated with nemaline myopathy: {alpha}-tropomyosin-3 (TPM3), {alpha}-actin (ACTA1), nebulin (NEB), {beta}-tropomysin (TPM2) and troponin T (TNNT1). In addition, mutations in the ryanodine receptor gene (RYR1) have been associated with core-rod myopathy. Here we report linkage in two unrelated families, with a variant of nemaline myopathy, with associated core-like lesions. The clinical phenotype consists of muscle weakness in addition to a peculiar kind of muscle slowness. A genome-wide scan revealed a locus for nemaline myopathy with core-like lesions on chromosome 15q21-q23 for both families. Combining the two families gave a two-point LOD score of 10.65 for D15S993. The {alpha}-tropomyosin-1 gene (TPM1) located within this region is the strongest candidate gene. However, no mutations were found in the protein-coding region of TPM1, although small deletions or mutations in an intron cannot be excluded. The critical region contains few other candidate genes coding for muscle proteins and several genes of unknown function, and has not yet been sequenced completely. The novel phenotype of nemaline myopathy in the two presented families corresponds to an also novel, as yet uncharacterized, genotype.

Keywords: nemaline; myopathy; genotype; core; chromosome 15
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Med. Genet.Home page
A M Kaindl, F Ruschendorf, S Krause, H-H Goebel, K Koehler, C Becker, D Pongratz, J Muller-Hocker, P Nurnberg, G Stoltenburg-Didinger, et al.
Missense mutations of ACTA1 cause dominant congenital myopathy with cores
J. Med. Genet., November 1, 2004; 41(11): 842 - 848.
[Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.