Novel valosin-containing protein mutations associated with multisystem proteinopathy
| Autor: | Sejad Al-Tahan, Matthew Wicklund, Bjarne Udd, Hiroshi Yoshioka, Lan Weiss, Molly Omizo, Yadollah Harati, Marjorie R. Grafe, Johanna Palmio, Virginia Kimonis, Ebaa Al-Obeidi, Anita Lakatos |
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| Přispěvatelé: | Medicum, Department of Medical and Clinical Genetics, University of Helsinki |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine p97 Parkinson's disease Bioinformatics 3124 Neurology and psychiatry AMYOTROPHIC-LATERAL-SCLEROSIS 0302 clinical medicine PARKINSONS-DISEASE Valosin Containing Protein Medicine Missense mutation INCLUSION-BODY MYOPATHY Amyotrophic lateral sclerosis 10. No inequality Genetics (clinical) biology Parkinson Disease Middle Aged Pedigree 3. Good health Multisystem proteinopathy Novel VCP mutations Neurology AAA-ATPASE CDC48/P97 medicine.symptom Inclusion body myopathy VCP GENE-MUTATIONS Frontotemporal dementia Adult Valosin-containing protein Mutation Missense ENDOPLASMIC-RETICULUM 03 medical and health sciences Muscular Diseases Humans Genetic Predisposition to Disease Myopathy Aged FRONTOTEMPORAL LOBAR DEGENERATION business.industry Amyotrophic Lateral Sclerosis 3112 Neurosciences Osteitis Deformans medicine.disease 030104 developmental biology Paget's disease of bone PAGET-DISEASE Pediatrics Perinatology and Child Health biology.protein Neurology (clinical) Age of onset DEMENTIA IBMPFD business VCP MUTATIONS 030217 neurology & neurosurgery |
| Popis: | Over fifty missense mutations in the gene coding for valosin-containing protein (VCP) are associated with a unique autosomal dominant adult-onset progressive disease associated with combinations of proximo-distal inclusion body myopathy (IBM), Paget's disease of bone (PDB), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). We report the clinical, histological, and molecular findings in four new patients/families carrying novel VCP mutations: c.474 G > A (p.M158I); c.478 G > C (p.A160P); c.383G > C (p.G128A); and c.382G > T (p.G128C). Clinical features included myopathy, PDB, ALS and Parkinson's disease though frontotemporal dementia was not an associated feature in these families. One of the patients was noted to have severe manifestations of PDB and was suspected of having neoplasia. There were wide inter- and intra-familial variations making genotype-phenotype correlations difficult between the novel mutations and frequency or age of onset of IBM, PDB, FTD, ALS and Parkinson's disease. Increasing awareness of the full spectrum of clinical presentations will improve diagnosis of VCP-related diseases and thus proactively manage or prevent associated clinical features such as PDB. (C) 2018 Published by Elsevier B.V. |
| Databáze: | OpenAIRE |
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