Novel valosin-containing protein mutations associated with multisystem proteinopathy.
Neuromuscul Disord
; 28(6): 491-501, 2018 06.
Article
en En
| MEDLINE
| ID: mdl-29754758
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteítis Deformante
/
Enfermedad de Parkinson
/
Mutación Missense
/
Proteína que Contiene Valosina
/
Esclerosis Amiotrófica Lateral
/
Enfermedades Musculares
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Aged
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Neuromuscul Disord
Asunto de la revista:
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM