VCP p.Arg191Gln mutation in a patient with semantic dementia: a case report

Area of Science:

• Neurogenetics
• Neurology
• Molecular Biology

Background:

• Valosin-containing protein (VCP) gene variants are linked to inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia (FTD).
• Pathogenic VCP variants typically manifest as behavioral-variant FTD (bvFTD) or, rarely, semantic dementia (SD).
• The VCP p.Arg155Cys variant is the only previously reported VCP mutation associated with SD.

Purpose of the Study:

• To report a novel case of semantic dementia (SD) caused by a pathogenic VCP variant.
• To investigate the phenotypic spectrum of VCP-related frontotemporal lobar degeneration (FTLD).

Main Methods:

• Case report of a Japanese female patient diagnosed with SD.
• Genetic analysis including whole-exome and Sanger sequencing to identify VCP variants.
• Clinical evaluation for neurological and systemic symptoms.

Main Results:

• A female patient presented with SD at age 56, characterized by language and behavioral changes.
• Genetic analysis revealed the novel pathogenic VCP variant p.Arg191Gln in the patient.
• The patient exhibited isolated SD without myopathy, pyramidal signs, or bone disease, progressing to severe disability and death.

Conclusions:

• The VCP p.Arg191Gln variant can cause isolated semantic dementia (SD).
• This case expands the known spectrum of frontotemporal lobar degeneration (FTLD) phenotypes associated with pathogenic VCP variants.
• VCP-related disorders encompass a broader range of FTLD presentations than previously recognized.