Neuropediatrics 2010; 41(1): 43-46
DOI: 10.1055/s-0030-1254101
Short Communication

© Georg Thieme Verlag KG Stuttgart · New York

Familial Reducing Body Myopathy with Cytoplasmic Bodies and Rigid Spine Revisited: Identification of a Second LIM Domain Mutation in FHL1

J. Schessl1 , 2 , A. Columbus2 , Y. Hu2 , Y. Zou2 , T. Voit3 , H. H. Goebel4 , C. G. Bönnemann2
  • 1Department of Neurology, Friedrich-Baur Institute, Munich, Germany
  • 2Department of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  • 3Institute of Myology, UPMC-Inserm-CNRS-AIM UMR 5974, U974, umr 7215, AP-HP, University Pierre et Marie Curie, Paris, France
  • 4Department of Neuropathology, Johannes Gutenberg University, Mainz, Germany
Further Information

Publication History

received 01.12.2009

accepted 19.04.2010

Publication Date:
22 June 2010 (online)

Abstract

Objective: Reducing body myopathy (RBM) is a rare progressive disorder of muscle characterized by intracytoplasmic inclusions, which stain strongly with menadione-NBT (nitroblue tetrazolium). We recently identified the four and a half LIM domain gene FHL1 located on chromosome Xq26 as the causative gene for RBM. So far eight familial cases and 21 sporadic patients with RBM have been reported in the literature.

Methods: We ascertained a total of 8 members of a German family initially reported by Goebel et al. as a mixed myopathy with rigid spine myopathy and reducing as well as cytoplasmic bodies. Clinical findings in the original and additional family members have been reviewed. Mutation detection was performed by direct sequencing of FHL1 exons.

Results: We identified a novel mutation (p.C150R) in the second LIM domain of FHL1 in six family members (1 male, 5 females). The male index patient was the most affected member presenting with rigid spine, followed by rapidly progressive muscle weakness. He died from the consequences of respiratory insufficiency at the age of 29.5 years. His sister, mother, grandmother, aunt and female cousin all carried the mutation in the heterozygous state. The sister is clinically unaffected; their mother had myopathic changes in her muscle biopsy, while the grandmother showed first signs of weakness at 50 years of age. The 54-year-old aunt and her daughter are clinically asymptomatic.

Conclusion: We report a novel LIM2 domain mutation in FHL1 in a previously reported family with RBM with cytoplasmic bodies and spinal rigidity. While the male index patient was significantly affected, female carriers show varying manifestations and may be asymptomatic, likely reflecting varying degrees of X-inactivation. RBM continues to be associated with mutations in the LIM2 domain of FHL1. We also confirm our earlier observation that mutations at the N-terminal end of the LIM2 domain seem to be milder compared to mutations seen at the C-terminal part of the domain which cause severe disease even in female carriers.

References

Correspondence

Joachim Schessl

Department of Neurology

Friedrich-Baur Institute

Ziemssenstraße 1A

80469 München

Germany

Phone: +49/089/5160 7470

Email: joachim.schessl@med.uni-muenchen.de

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