A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Fanganiello, Roberto Dalto; Kimonis, Virginia; Côrte, C C; Nitrini, Ricardo; Passos‐Bueno, Maria Rita

doi:10.1590/s0100-879x2011007500028

Cited by 25 publications

(20 citation statements)

References 19 publications

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“…Patient 2 had parallel findings of MRI and dementia. Although a discrepancy between imaging findings and symptoms was present, the common and characteristic finding in our patients was hippocampal atrophy, consistent with a finding in reported patients with VCP -related IBMPFD [8] .…”

Section: Discussionsupporting

confidence: 88%

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Time Course of Radiological Imaging and Variable Interindividual Symptoms in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated with p.Arg487His Mutation in the VCP Gene

et al. 2017

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To our knowledge, this is the first study to report the time course of radiological imaging of 3 patients from 2 families with VCP-related amyotrophic lateral sclerosis (ALS) and dementia. Both families shared the same p.Arg487His mutation in the VCP gene encoding valosin-containing protein. The first patient started to have a typical form of ALS, followed by dementia 7 years later. The second patient, a brother of the first one, had frontotemporal dementia and parkinsonism. The third patient had simultaneous ALS and dementia. All patients seemed to have progressive brain atrophy as their clinical symptoms progressed. The common and characteristic finding was atrophy of the temporal lobes including the hippocampi. The relation between imaging findings and symptoms varied considerably among the 3 patients.

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Section: Discussionsupporting

confidence: 88%

“…Reported findings of imaging in VCP -related disorders were limited in patients with IBMPFD [7,8] , and the imaging time course has been described only in 1 patient [7] . Patients 1 and 2 had apparent atrophy of the frontal and temporal lobes, and patient 2 had atrophy already 2 years after onset.…”

Section: Discussionmentioning

confidence: 99%

Time Course of Radiological Imaging and Variable Interindividual Symptoms in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated with p.Arg487His Mutation in the VCP Gene

et al. 2017

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“…With greater than 27 mutations having been identified, VCP-associated disease is increasingly being recognized worldwide [8] in families from Germany [9], [10], France [11], Austria [12], Italy [13], [14], the UK [15], Australia [16], Brazil [17], Korea and the US [18], [19]. Most mutations occur in the ubiquitin binding domain of VCP with the R155H mutation being the most common mutation, accounting for approximately half of the affected individuals [2], [20], [21].…”

Section: Introductionmentioning

confidence: 99%

Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease

et al. 2013

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BackgroundThe therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP) gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) and more recently affect 2% of amyotrophic lateral sclerosis (ALS)-diagnosed cases.Methods/Principle FindingsThe present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCPR155H/+ mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCPR155H/+ mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype.ConclusionsCollectively, our data highlights that uphill exercise training in VCPR155H/+ mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases.

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“…Mutations in VCP are primarily in the N-terminal domain involved in ubiquitin binding and protein-protein interactions [6], [16], however mutations in other domains have also been identified. VCP-associated disease is increasingly being recognized worldwide, with 26 mutations having been identified thus far in families from Germany [17], [18], France [19], Austria [20], Italy [21], [22], UK [23], Australia [24], Brazil [25], Korea [26], [27] and the US [28], [29]. The R155H mutation is by far the most common, accounting for approximately 50% of affected individuals [1], [6], [30].…”

Section: Introductionmentioning

confidence: 99%

The Homozygote VCPR155H/R155H Mouse Model Exhibits Accelerated Human VCP-Associated Disease Pathology

et al. 2012

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Valosin containing protein (VCP) mutations are the cause of hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia (IBMPFD). VCP gene mutations have also been linked to 2% of isolated familial amyotrophic lateral sclerosis (ALS). VCP is at the intersection of disrupted ubiquitin proteasome and autophagy pathways, mechanisms responsible for the intracellular protein degradation and abnormal pathology seen in muscle, brain and spinal cord. We have developed the homozygous knock-in VCP mouse (VCPR155H/R155H) model carrying the common R155H mutations, which develops many clinical features typical of the VCP-associated human diseases. Homozygote VCPR155H/R155H mice typically survive less than 21 days, exhibit weakness and myopathic changes on EMG. MicroCT imaging of the bones reveal non-symmetrical radiolucencies of the proximal tibiae and bone, highly suggestive of PDB. The VCPR155H/R155H mice manifest prominent muscle, heart, brain and spinal cord pathology, including striking mitochondrial abnormalities, in addition to disrupted autophagy and ubiquitin pathologies. The VCPR155H/R155H homozygous mouse thus represents an accelerated model of VCP disease and can be utilized to elucidate the intricate molecular mechanisms involved in the pathogenesis of VCP-associated neurodegenerative diseases and for the development of novel therapeutic strategies.

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A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Cited by 25 publications

References 19 publications

Time Course of Radiological Imaging and Variable Interindividual Symptoms in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated with p.Arg487His Mutation in the <b><i>VCP</i></b> Gene

Time Course of Radiological Imaging and Variable Interindividual Symptoms in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Associated with p.Arg487His Mutation in the <b><i>VCP</i></b> Gene

Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease

The Homozygote VCPR155H/R155H Mouse Model Exhibits Accelerated Human VCP-Associated Disease Pathology

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