Your browser doesn't support javascript.
loading
Muscle and nerve pathology in Dunnigan familial partial lipodystrophy.
Spuler, S; Kalbhenn, T; Zabojszcza, J; van Landeghem, F K H; Ludtke, A; Wenzel, K; Koehnlein, M; Schuelke, M; Lüdemann, L; Schmidt, H H.
Afiliação
  • Spuler S; Muscle Research Group, Department of Neurology, Medical Faculty of the Charité, Berlin, Germany. simone.spuler@charite.de
Neurology ; 68(9): 677-83, 2007 Feb 27.
Article em En | MEDLINE | ID: mdl-17325275
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.
Assuntos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Crescimento Transformador beta / Doenças do Sistema Nervoso Periférico / Proteínas Smad / Lipodistrofia Parcial Familiar / Doenças Musculares Limite: Adult / Female / Humans / Male Idioma: En Revista: Neurology Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Alemanha
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Crescimento Transformador beta / Doenças do Sistema Nervoso Periférico / Proteínas Smad / Lipodistrofia Parcial Familiar / Doenças Musculares Limite: Adult / Female / Humans / Male Idioma: En Revista: Neurology Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Alemanha