Novel valosin-containing protein mutations associated with multisystem proteinopathy

Sejad Al-Tahan, Ebaa Al-Obeidi, Hiroshi Yoshioka, Anita Lakatos, Lan Weiss, Marjorie Grafe, Johanna Palmio, Matt Wicklund, Yadollah Harati, Molly Omizo, Bjarne Udd, Virginia Kimonis

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalNeuromuscular Disorders
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Inclusion body myopathy
  • Novel VCP mutations
  • p97
  • Paget's disease of bone
  • Parkinson's disease
  • VCP

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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    Al-Tahan, S., Al-Obeidi, E., Yoshioka, H., Lakatos, A., Weiss, L., Grafe, M., Palmio, J., Wicklund, M., Harati, Y., Omizo, M., Udd, B., & Kimonis, V. (Accepted/In press). Novel valosin-containing protein mutations associated with multisystem proteinopathy. Neuromuscular Disorders. https://doi.org/10.1016/j.nmd.2018.04.007