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Muscle and nerve pathology in Dunnigan familial partial lipodystrophy

Item Type:Article
Title:Muscle and nerve pathology in Dunnigan familial partial lipodystrophy
Creators Name:Spuler, S. and Kalbhenn, T. and Zabojszcza, J. and van Landeghem, F.K. and Ludtke, A. and Wenzel, K. and Koehnlein, M. and Schuelke, M. and Luedemann, L. and Schmidt, H.H.
Abstract: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.
Keywords:Familial Partial Lipodystrophy, Muscular Diseases, Myostatin, Peripheral Nervous System Diseases, Skeletal Muscle, Smad Proteins, Sural Nerve, Transforming Growth Factor beta
Publisher:American Academy of Neurology
Page Range:677-683
Date:27 February 2007
Official Publication:https://doi.org/10.1212/01.wnl.0000255939.73424.f8
PubMed:View item in PubMed

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