A Novel Mutation (D395A) in Valosin-Containing Protein Gene Is Associated With Early Onset Frontotemporal Dementia in an Italian Family.

Abstract

Inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and/or frontotemporal dementia (FTD) (IBMPFD) was recently identified as rare autosomal dominant disorder due to mutations in VCP gene. However, VCP mutations have also been documented in patients with amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth type 2 (CMT2) disease, and hereditary spastic paraplegia (HSP), underlining the heterogeneity of the phenotypes due to VCP mutations. In this study, we reported a novel missense heterozygous variant c.1184A > C (p.D395A) in exon 10 of VCP gene identified in three patients (two sisters and one brother) belonging to an Italian family. The patients underwent a detailed clinical evaluation including medical history, neurological examination, and neuropsychological assessment. Brain's morphologic and functional analysis was also performed. The whole picture was consistent with the criteria of behavioral variant frontotemporal dementia (bvFTD) without IBM and PBD. Our report confirms the high degree of heterogeneity of VCP disease. A VCP analysis should be considered for the genetic screening of familial bvFTD with an early onset also in absence of IBM or PDB signs.

• Authors: Francesco Bruno, Maria Elena Conidi, Gianfranco Puccio, Francesca Frangipane, Valentina Laganà, Livia Bernardi, Nicoletta Smirne, Maria Mirabelli, Rosanna Colao, Sabrina Curcio, Raffaele Di Lorenzo, Raffaele Maletta, Amalia Cecilia Bruni
• Journal: Frontiers in genetics (Front Genet) Vol. 12 Pg. 795029 ( 2021) ISSN: 1664-8021 [Print] Switzerland
• PMID: 34917136 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Bruno, Conidi, Puccio, Frangipane, Laganà, Bernardi, Smirne, Mirabelli, Colao, Curcio, Di Lorenzo, Maletta and Bruni.