Muscle and nerve pathology in Dunnigan familial partial lipodystrophy.
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
/
Doenças do Sistema Nervoso Periférico
/
Proteínas Smad
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Lipodistrofia Parcial Familiar
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Doenças Musculares
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurology
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Alemanha