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Genotype-phenotype correlations in valosin-containing protein disease
- Source :
- JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, Journal of neurology, neurosurgery and psychiatry, Journal of Neurology, Neurosurgery and Psychiatry, 93(10), 1099-1111. BMJ PUBLISHING GROUP, Journal of Neurology, Neurosurgery and Psychiatry, 93(10):328921, 1099-1111. BMJ Publishing Group
- Publication Year :
- 2022
-
Abstract
- [ntroduction] Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations.<br />[Methods] Descriptive retrospective study collecting clinical and genetic data from patients with confirmed mutations in the VCP gene in 52 centres from 24 countries.<br />[Results] We included 234 patients (70% males, mean age 55.54 + 9.6 years [y]). Mean age at symptom onset 45.6 + 9.3 y, mean diagnostic delay 7.74 + 6 y, and mean time of disease progression 11.3 + 6.9 y. Disease onset was symmetric lower limb weakness in 50% of the patients progressing towards generalized muscle weakness affecting proximal and distal lower and upper limb muscles. Other clinical features included: respiratory symptoms in 40.3%, PBD in 26.7%, dysautonomia in 21.4%, upper and lower motor neuron signs in 13.3% and 21.85%, and FTD in 13.9% of the patient. Fifty-eight genetic variants were identified being the most frequent the c.464G>A, p.Arg155His in 28% of the patients and the c.463C>T, p.Arg155Cys in 11.1%. Twenty new mutations were identified. The c.463C>T, p.Arg155Cys variant had the earliest age of onset (37.8 + 7.6 y) among the 4 most frequent variants and a higher frequency of axial weakness, distal upper limb weakness, scapula winging and mix cognitive. 19.1% of the patients were full time wheelchair users and 4.0% (9/225) were bedridden at a median of 8.5 y and 15 y from onset. Thirty–seven patients died at a mean age of 63.9 + 8.1 and at a mean of 15.8 + 6.6 y from disease onset, 7 due to respiratory insufficiency and 5 due to rapidly progressive dementia. The presence of a FVC< 50% was associated with being full time wheelchair user/ bedridden and the presence of a FVC<br />[Conclusion] The heterogeneous clinical features of VCP could resemble other neuromuscular conditions. The c.463C>T p.Arg155Cys variant seems to have an earlier age of onset and more severe phenotype. Presence of FVC
Details
- Language :
- English
- ISSN :
- 00223050
- Database :
- OpenAIRE
- Journal :
- JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, Journal of neurology, neurosurgery and psychiatry, Journal of Neurology, Neurosurgery and Psychiatry, 93(10), 1099-1111. BMJ PUBLISHING GROUP, Journal of Neurology, Neurosurgery and Psychiatry, 93(10):328921, 1099-1111. BMJ Publishing Group
- Accession number :
- edsair.doi.dedup.....2f2d1f3b8c1678f2ecadb77fcd371913