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 language | English (US) |
|---|---|
| Journal | Neuromuscular Disorders |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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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)
Cite this
Novel valosin-containing protein mutations associated with multisystem proteinopathy. / Al-Tahan, Sejad; Al-Obeidi, Ebaa; Yoshioka, Hiroshi; Lakatos, Anita; Weiss, Lan; Grafe, Marjorie; Palmio, Johanna; Wicklund, Matt; Harati, Yadollah; Omizo, Molly; Udd, Bjarne; Kimonis, Virginia.
In: Neuromuscular Disorders, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel valosin-containing protein mutations associated with multisystem proteinopathy
AU - Al-Tahan, Sejad
AU - Al-Obeidi, Ebaa
AU - Yoshioka, Hiroshi
AU - Lakatos, Anita
AU - Weiss, Lan
AU - Grafe, Marjorie
AU - Palmio, Johanna
AU - Wicklund, Matt
AU - Harati, Yadollah
AU - Omizo, Molly
AU - Udd, Bjarne
AU - Kimonis, Virginia
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Inclusion body myopathy
KW - Novel VCP mutations
KW - p97
KW - Paget's disease of bone
KW - Parkinson's disease
KW - VCP
UR - http://www.scopus.com/inward/record.url?scp=85046882286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046882286&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2018.04.007
DO - 10.1016/j.nmd.2018.04.007
M3 - Article
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
ER -