A cross-sectional analysis of clinical evaluation in 35 individuals with mutations of the valosin-containing protein gene

Plewa, Jake; Surampalli, Abhilasha; Wencel, Marie; Milad, Merit; Donkervoort, Sandra; Caiozzo, Vincent J.; Goyal, Namita; Mozaffar, Tahseen; Kimonis, Virginia

doi:10.1016/j.nmd.2018.06.007

Cited by 8 publications

(21 citation statements)

References 62 publications

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“…Both questionnaire and examination including IBMFRS/MRC scale suggested involvement of both proximal/distal muscle weakness and predominance of the lower extremity weakness without any muscle sparing. In a previous study, correlation between IBMFRS and MRC scale/fatigue scale/6-min walk test in patients with mutations of the VCP gene was detected [27]. The results in this study also support the idea that IBMFRS may correlate with MRC scale in that both suggested the predominance of the lower extremity weakness and that the IBMFRS could be useful for assessing the muscle weakness in the patients with VCP gene mutations.…”

Section: Discussionsupporting

confidence: 85%

“…In French and Spanish cohort, 29% of the patients showed a forced vital capacity under 70% of the predicted value [2]. In a second study, the forced vital capacity as a percentage of the individual's reference value, was 84.44 ± 29.53 (mean ± SD, %) [27]. The results in this study also suggest the effect on inspiratory muscles and respiratory function should be monitored regularly.…”

Section: Discussionsupporting

confidence: 48%

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Phenotypic diversity in an international Cure VCP Disease registry

Ikenaga

Findlay

Seiffert

et al. 2020

Orphanet J Rare Dis

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Background Dominant mutations in valosin-containing protein (VCP) gene cause an adult onset inclusion body myopathy, Paget’s disease of bone, and frontotemporal dementia also termed multisystem proteinopathy (MSP). The genotype-phenotype relationships in VCP-related MSP are still being defined; in order to understand this better, we investigated the phenotypic diversity and patterns of weakness in the Cure VCP Disease Patient Registry. Methods Cure VCP Disease, Inc. was founded in 2018 for the purpose of connecting patients with VCP gene mutations and researchers to help advance treatments and cures. Cure VCP Disease Patient Registry is maintained by Coordination of Rare Diseases at Sanford. The results of two questionnaires with a 5-point Likert scale questions regarding to patients’ disease onset, symptoms, and daily life were obtained from 59 participants (28 males and 31 females) between June 2018 and May 2020. Independent of the registry, 22 patients were examined at the Cure VCP Disease annual patient conference in 2019. Results In the questionnaires of the registry, fifty-three patients (90%) reported that they were with inclusion body myopathy, 17 patients (29%) with Paget’s disease of bone, eight patients (14%) with dementia, two patients (3%) with amyotrophic lateral sclerosis, and a patient with parkinsonism. Thirteen patients (22%) reported dysphagia and 25 patients (42%) reported dyspnea on exertion. A self-reported functional rating scale for motor function identified challenges with sit to stand (72%), walking (67%), and climbing stairs (85%). Thirty-five (59%) patients in the registry answered that their quality of life is more than good. As for the weakness pattern of the 22 patients who were evaluated at the Cure VCP Disease annual conference, 50% of patients had facial weakness, 55% had scapular winging, 68% had upper proximal weakness, 41% had upper distal weakness, 77% had lower proximal, and 64% had lower distal weakness. Conclusions The Cure VCP Disease Patient Registry is useful for deepening the understanding of patient daily life, which would be a basis to develop appropriate clinical outcome measures. The registry data is consistent with previous studies evaluating VCP patients in the clinical setting. Patient advocacy groups are essential in developing and maintaining disease registries.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 48%

Phenotypic diversity in an international Cure VCP Disease registry

Ikenaga

Findlay

Seiffert

et al. 2020

Orphanet J Rare Dis

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“…A recent study by Al-Obeidi et al (2018) showed that VCP mutations are present in ∼9% of ALS, 4% of Parkinson's disease, and 2% of Alzheimer's disease patients. As of today, no definite correlation between the mutation type and the incidence of clinical features associated with VCP has been established (Al-Obeidi et al, 2018;Plewa et al, 2018).…”

Section: Valosin Containing Protein (Vcp)mentioning

confidence: 99%

The Overlapping Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

et al. 2020

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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two diseases that form a broad neurodegenerative continuum. Considerable effort has been made to unravel the genetics of these disorders, and, based on this work, it is now clear that ALS and FTD have a significant genetic overlap. TARDBP, SQSTM1, VCP, FUS, TBK1, CHCHD10, and most importantly C9orf72, are the critical genetic players in these neurological disorders. Discoveries of these genes have implicated autophagy, RNA regulation, and vesicle and inclusion formation as the central pathways involved in neurodegeneration. Here we provide a summary of the significant genes identified in these two intrinsically linked neurodegenerative diseases and highlight the genetic and pathological overlaps.

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“…Grip strength measurements using the Jamar handheld dynamometer (Patterson Medical) was obtained at five time points at UC Irvine Institute of Clinical Translational Science (ICTS), and at weekly intervals by the patient using a Camry® EH101 electronic hand dynamometer. Dynamometry is an effective for assessing isometric limb strength and is correlated with the IBMFRS scale [4,7].…”

Section: Grip Strength Dynamometrymentioning

confidence: 99%

“…Frontotemporal dementia which occurs at a mean age of 55 years in 30% of IBMPFD patients often results in early death; however, those with myopathy may have several decades of increasing weakness and loss of mobility. IBMPFD is highly penetrant and is typically considered if two or more of the typical features or suggestive family history is present [4]. There is currently a lack of information on the long-term progression of this disease.…”

Section: Introductionmentioning

confidence: 99%

A Natural History Study of VCP Associated Vacuolar Myopathy in a Patient with the Common R155H Mutation

Sweetman¹,

Plewa²,

Nguyen³

et al. 2020

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Background: IBMPFD (Inclusion Body Myopathy associated with Paget disease of the bone and Frontotemporal Dementia) is an autosomal dominant inherited disease caused by VCP gene mutations. Very little natural history data exists on this disease. We report a patient with a significant family history of IBMPFD associated with the common R155H mutation in the VCP gene. Objective: This study will address the lack of long-term data for muscle strength, and respiratory function in IBMPFD. The hypothesis is that detailed analysis in a single patient will provide meaningful natural history data in IBMPFD, a progressive neurodegenerative disease. Method: Regression analysis was performed across multiple parameters related to myopathy including dynamometry, MRC scale, IBM functional rating scale, pulmonary function studies and sleep quality. Results: Measurements of this patient highlight progressive generalized weakness in proximal and distal regions, decline in pulmonary function, and asymmetrical strength differences of the upper extremities. Measurements over five years revealed an overall deterioration with a slope of -1.13 and R2 value of 0.77. Conclusion: This unique data derived from long-term evaluations in a patient provides the first report of the rate of progression of muscle weakness and pulmonary function deterioration in VCP associated inclusion body myopathy.

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A cross-sectional analysis of clinical evaluation in 35 individuals with mutations of the valosin-containing protein gene

Cited by 8 publications

References 62 publications

Phenotypic diversity in an international Cure VCP Disease registry

Phenotypic diversity in an international Cure VCP Disease registry

The Overlapping Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

A Natural History Study of VCP Associated Vacuolar Myopathy in a Patient with the Common R155H Mutation

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