An unusual familial dementia associated with G131V PRNP mutation

Background Gerstmann‐Struassler‐Scheinker disease is one of the familial prion diseases secondary to mutations in the prion protein gene ( PRNP ). The clinical phenotype has a diverse spectrum and might show variation among cases with the same genotype. We report a patient with G131V mutation in the PRNP gene, who was initially considered to harbor familial Alzheimer’s disease, based on the family history, clinical presentation and imaging findings. Methods A case with a G131V mutation in the PRNP gene is described, and the literature is reviewed. Results A 35‐year‐old man presented with personality changes, behavioral disturbances and cognitive complaints. A similar clinical phenotype was reported in the patient’s father, a paternal uncle and a paternal aunt. In conjunction with the observation of mild cerebral atrophy on magnetic resonance imaging and hypometabolism in bilateral temporal and parietal lobes on positron‐emission tomography studies, the diagnosis was initially considered as familial Alzheimer’s disease. However, whole‐exome sequencing of the index patient, confirmed with Sanger sequencing in his father and uncle, revealed the presence of a heterozygous G131V variant in the PRNP gene. Conclusion To the best of our knowledge, this is the third report of a G131V mutation in the PRNP gene in the literature. Although ataxia and extrapyramidal findings accompanied dementia in patients reported in the previous literature, the members of the family in the present case primarily reported cognitive impairment, underscoring the importance of genetic evaluation in familial early‐onset dementia patients, regardless of clinical and imaging features suggestive of alternative pathologies.