Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow CME: Take the course for this article:
 Volume 68, Number 9, February 27, 2007
Right arrow Videos
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Spuler, S.
Right arrow Articles by Schmidt, H. H.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Spuler, S.
Right arrow Articles by Schmidt, H. H.
NEUROLOGY 2007;68:677-683
© 2007 American Academy of Neurology

Muscle and nerve pathology in Dunnigan familial partial lipodystrophy

S. Spuler, MD, T. Kalbhenn, MD, J. Zabojszcza, MS, F.K.H. van Landeghem, MD, A. Ludtke, MD, K. Wenzel, PhD, M. Koehnlein, MD, M. Schuelke, MD, L. Lüdemann, MD and H. H. Schmidt, MD

From the Muscle Research Group, Department of Neurology (S.S., J.Z., K.W., M.K.), Department of Neurosurgery (T.K.), Institute for Neuropathology (F.K.H.v.L.), Department of Hepatology, Endocrinology and Gastroenterology (A.L., H.H.S.), Department of Neuropediatrics (M.S.), and Department of Radiation Medicine (L.L.), Medical Faculty of the Charité, Berlin, Germany is currently with the Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY. H.H.S. is currently with the Hepatology Section, University of Münster, Germany.

Address correspondence and reprint requests to Dr. Simone Spuler, Department of Neurology, Charité University Hospital, Augustenburger Platz 1, D-13353 Berlin, Germany; e-mail: simone.spuler{at}charite.de

Objective: To characterize muscle and nerve pathology in Dunnigan familial partial lipodystrophy (FPLD).

Methods: We used conventional histology, immunohistochemistry, messenger RNA (mRNA) expression, gene sequencing, and clinical studies of 13 patients with neuromuscular involvement.

Results: The clinical findings consisted of muscle hypertrophy (12/13), severe myalgias (9/13), and multiple nerve entrapment syndromes (8/13). Skeletal muscle histology demonstrated marked Type 1 and 2 muscle fiber hypertrophy and nonspecific myopathic changes, whereas numerous paranodal myelin swellings (tomacula) were found in sural nerve biopsies. We found that myostatin mRNA expression was reduced in patients with FPLD vs controls. We sequenced the myostatin gene in our subjects, but found no mutations. We then investigated whether or not SMAD, the intracellular mediator of myostatin signaling, might be impaired in patients with FPLD. We found that in FPLD muscle, a large number of SMAD molecules adhered to the nuclear membrane and were not found within the nucleus, compared with normal muscle or muscle from a patient with a non-FPLD lamin A/C disease.

Conclusion: The myopathy and neuropathy associated with Dunnigan familial partial lipodystrophy are distinct from other lamin A/C disorders. We hypothesize that the lipodystrophy-associated mutation interferes with SMAD signaling, linking this type of lipodystrophy to the phenotypically similar myostatin deficiency.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the February 27 issue to find the title link for this article.

Disclosure: The authors report no conflicts of interest.

Received April 6, 2006. Accepted in final form November 7, 2006.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by AAN Enterprises, Inc.