A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
Braz. j. med. biol. res
; 44(4): 374-380, Apr. 2011. ilus, tab
Article
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| ID: lil-581492
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BR1.1
ABSTRACT
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.
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LILACS
Asunto principal:
Osteítis Deformante
/
Adenosina Trifosfatasas
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Proteínas de Ciclo Celular
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Miositis por Cuerpos de Inclusión
/
Demencia Frontotemporal
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Estudios de Asociación Genética
/
Mutación
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
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Aged80
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Female
/
Humans
/
Male
País/Región como asunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Braz. j. med. biol. res
Asunto de la revista:
BIOLOGIA
/
MEDICINA
Año:
2011
Tipo del documento:
Article