Phenotypic variability in three families with valosin-containing protein mutation

S. Spina, A. D. Van Laar, J. R. Murrell, R. L. Hamilton, J. K. Kofler, F. Epperson, Martin Farlow, O. L. Lopez, J. Quinlan, S. T. Dekosky, Bernardino Ghetti

Research output: Contribution to journalArticle

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Abstract

Background and purpose: The phenotype of IBMPFD [inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (FTD)] associated with valosin-containing protein (VCP) mutation is described in three families. Methods: Probands were identified based on a pathological diagnosis of frontotemporal lobar degeneration with TDP-43-positive inclusions type IV. VCP sequencing was carried out. Clinical data on affected family members were reviewed. Results: Ohio family: four subjects presented muscle weakness and wasting. (One subject had both neuropathic and myopathic findings and another subject showed only evidence of myopathy. The etiology of weakness could not be ascertained in the remaining two subjects.) Two individuals also showed Parkinsonism (with associated FTD in one of the two). The proband's brain displayed FTLD-TDP type IV and Braak stage five Parkinson's disease (PD). A VCP R191Q mutation was found. Pennsylvania family: 11 subjects developed IBMPFD. Parkinsonism was noted in two mutation carriers, whilst another subject presented with primary progressive aphasia (PPA). A novel VCP T262A mutation was found. Indiana family: three subjects developed IBMPFD. FTD was diagnosed in two individuals and suspected in the third one who also displayed muscle weakness. A VCP R159C mutation was found. Conclusions: We identified three families with IBMPFD associated with VCP mutations. Clinical and pathological PD was documented for the first time in members of two families. A novel T262A mutation was found. One individual had PPA: an uncommon presentation of IBMPFD.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalEuropean Journal of Neurology
Volume20
Issue number2
DOIs
StatePublished - Feb 2013

Fingerprint

Frontotemporal Dementia
Mutation
Primary Progressive Aphasia
Muscle Weakness
Muscular Diseases
Parkinson Disease
Frontotemporal Lobar Degeneration
Osteitis Deformans
Inclusion Bodies
Protein Sequence Analysis
Parkinsonian Disorders
CDC48 protein
Inclusion Body Myopathy With Early-Onset Paget Disease And Frontotemporal Dementia
Phenotype
Brain

Keywords

  • Frontotemporal dementia
  • Genetic and inherited disorders
  • Motor neuron disease
  • Myopathies
  • Neurodegenerative disorders (other than dementia)
  • Neuropathology
  • Neuropsychology
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Spina, S., Van Laar, A. D., Murrell, J. R., Hamilton, R. L., Kofler, J. K., Epperson, F., ... Ghetti, B. (2013). Phenotypic variability in three families with valosin-containing protein mutation. European Journal of Neurology, 20(2), 251-258. https://doi.org/10.1111/j.1468-1331.2012.03831.x

Phenotypic variability in three families with valosin-containing protein mutation. / Spina, S.; Van Laar, A. D.; Murrell, J. R.; Hamilton, R. L.; Kofler, J. K.; Epperson, F.; Farlow, Martin; Lopez, O. L.; Quinlan, J.; Dekosky, S. T.; Ghetti, Bernardino.

In: European Journal of Neurology, Vol. 20, No. 2, 02.2013, p. 251-258.

Research output: Contribution to journalArticle

Spina, S, Van Laar, AD, Murrell, JR, Hamilton, RL, Kofler, JK, Epperson, F, Farlow, M, Lopez, OL, Quinlan, J, Dekosky, ST & Ghetti, B 2013, 'Phenotypic variability in three families with valosin-containing protein mutation', European Journal of Neurology, vol. 20, no. 2, pp. 251-258. https://doi.org/10.1111/j.1468-1331.2012.03831.x
Spina, S. ; Van Laar, A. D. ; Murrell, J. R. ; Hamilton, R. L. ; Kofler, J. K. ; Epperson, F. ; Farlow, Martin ; Lopez, O. L. ; Quinlan, J. ; Dekosky, S. T. ; Ghetti, Bernardino. / Phenotypic variability in three families with valosin-containing protein mutation. In: European Journal of Neurology. 2013 ; Vol. 20, No. 2. pp. 251-258.
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abstract = "Background and purpose: The phenotype of IBMPFD [inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (FTD)] associated with valosin-containing protein (VCP) mutation is described in three families. Methods: Probands were identified based on a pathological diagnosis of frontotemporal lobar degeneration with TDP-43-positive inclusions type IV. VCP sequencing was carried out. Clinical data on affected family members were reviewed. Results: Ohio family: four subjects presented muscle weakness and wasting. (One subject had both neuropathic and myopathic findings and another subject showed only evidence of myopathy. The etiology of weakness could not be ascertained in the remaining two subjects.) Two individuals also showed Parkinsonism (with associated FTD in one of the two). The proband's brain displayed FTLD-TDP type IV and Braak stage five Parkinson's disease (PD). A VCP R191Q mutation was found. Pennsylvania family: 11 subjects developed IBMPFD. Parkinsonism was noted in two mutation carriers, whilst another subject presented with primary progressive aphasia (PPA). A novel VCP T262A mutation was found. Indiana family: three subjects developed IBMPFD. FTD was diagnosed in two individuals and suspected in the third one who also displayed muscle weakness. A VCP R159C mutation was found. Conclusions: We identified three families with IBMPFD associated with VCP mutations. Clinical and pathological PD was documented for the first time in members of two families. A novel T262A mutation was found. One individual had PPA: an uncommon presentation of IBMPFD.",
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AU - Van Laar, A. D.

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AU - Hamilton, R. L.

AU - Kofler, J. K.

AU - Epperson, F.

AU - Farlow, Martin

AU - Lopez, O. L.

AU - Quinlan, J.

AU - Dekosky, S. T.

AU - Ghetti, Bernardino

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N2 - Background and purpose: The phenotype of IBMPFD [inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (FTD)] associated with valosin-containing protein (VCP) mutation is described in three families. Methods: Probands were identified based on a pathological diagnosis of frontotemporal lobar degeneration with TDP-43-positive inclusions type IV. VCP sequencing was carried out. Clinical data on affected family members were reviewed. Results: Ohio family: four subjects presented muscle weakness and wasting. (One subject had both neuropathic and myopathic findings and another subject showed only evidence of myopathy. The etiology of weakness could not be ascertained in the remaining two subjects.) Two individuals also showed Parkinsonism (with associated FTD in one of the two). The proband's brain displayed FTLD-TDP type IV and Braak stage five Parkinson's disease (PD). A VCP R191Q mutation was found. Pennsylvania family: 11 subjects developed IBMPFD. Parkinsonism was noted in two mutation carriers, whilst another subject presented with primary progressive aphasia (PPA). A novel VCP T262A mutation was found. Indiana family: three subjects developed IBMPFD. FTD was diagnosed in two individuals and suspected in the third one who also displayed muscle weakness. A VCP R159C mutation was found. Conclusions: We identified three families with IBMPFD associated with VCP mutations. Clinical and pathological PD was documented for the first time in members of two families. A novel T262A mutation was found. One individual had PPA: an uncommon presentation of IBMPFD.

AB - Background and purpose: The phenotype of IBMPFD [inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (FTD)] associated with valosin-containing protein (VCP) mutation is described in three families. Methods: Probands were identified based on a pathological diagnosis of frontotemporal lobar degeneration with TDP-43-positive inclusions type IV. VCP sequencing was carried out. Clinical data on affected family members were reviewed. Results: Ohio family: four subjects presented muscle weakness and wasting. (One subject had both neuropathic and myopathic findings and another subject showed only evidence of myopathy. The etiology of weakness could not be ascertained in the remaining two subjects.) Two individuals also showed Parkinsonism (with associated FTD in one of the two). The proband's brain displayed FTLD-TDP type IV and Braak stage five Parkinson's disease (PD). A VCP R191Q mutation was found. Pennsylvania family: 11 subjects developed IBMPFD. Parkinsonism was noted in two mutation carriers, whilst another subject presented with primary progressive aphasia (PPA). A novel VCP T262A mutation was found. Indiana family: three subjects developed IBMPFD. FTD was diagnosed in two individuals and suspected in the third one who also displayed muscle weakness. A VCP R159C mutation was found. Conclusions: We identified three families with IBMPFD associated with VCP mutations. Clinical and pathological PD was documented for the first time in members of two families. A novel T262A mutation was found. One individual had PPA: an uncommon presentation of IBMPFD.

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