| Registro completo |
| Provedor de dados: |
BJMBR
|
| País: |
Brazil
|
| Título: |
A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
|
| Autores: |
Fanganiello,R.D.
Kimonis,V.E.
Côrte,C.C.
Nitrini,R.
Passos-Bueno,M.R.
|
| Data: |
2011-04-01
|
| Ano: |
2011
|
| Palavras-chave: |
Frontotemporal dementia
VCP gene mutations
Myopathy
Paget disease of bone
|
| Resumo: |
Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.
|
| Tipo: |
Info:eu-repo/semantics/article
|
| Idioma: |
Inglês
|
| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000400016
|
| Editor: |
Associação Brasileira de Divulgação Científica
|
| Relação: |
10.1590/S0100-879X2011007500028
|
| Formato: |
text/html
|
| Fonte: |
Brazilian Journal of Medical and Biological Research v.44 n.4 2011
|
| Direitos: |
info:eu-repo/semantics/openAccess
|
