A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
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 frontote...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2011-04-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000400016 |
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| author | R.D. Fanganiello V.E. Kimonis C.C. Côrte R. Nitrini M.R. Passos-Bueno |
| author_facet | R.D. Fanganiello V.E. Kimonis C.C. Côrte R. Nitrini M.R. Passos-Bueno |
| author_sort | R.D. Fanganiello |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T00:24:13Z |
| format | Article |
| id | doaj.art-f576541f3f5e4108b7b82fed9588a192 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-04-14T00:24:13Z |
| publishDate | 2011-04-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-f576541f3f5e4108b7b82fed9588a1922022-12-22T02:22:50ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2011-04-01444374380A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementiaR.D. FanganielloV.E. KimonisC.C. CôrteR. NitriniM.R. Passos-BuenoInclusion 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000400016Frontotemporal dementiaVCP gene mutationsMyopathyPaget disease of bone |
| spellingShingle | R.D. Fanganiello V.E. Kimonis C.C. Côrte R. Nitrini M.R. Passos-Bueno A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia Brazilian Journal of Medical and Biological Research Frontotemporal dementia VCP gene mutations Myopathy Paget disease of bone |
| title | A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia |
| title_full | A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia |
| title_fullStr | A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia |
| title_full_unstemmed | A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia |
| title_short | A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia |
| title_sort | brazilian family with hereditary inclusion body myopathy associated with paget disease of bone and frontotemporal dementia |
| topic | Frontotemporal dementia VCP gene mutations Myopathy Paget disease of bone |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000400016 |
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