Genetic Creutzfeldt‒Jakob disease with 5-octapeptide repeats presented as frontotemporal dementia

Area of Science:

• Neurogenetics
• Prion Biology
• Molecular Neurology

Background:

• The PRNP gene's N-terminus typically has a 5-octapeptide repeat (R1-R2-R2-R3-R4).
• Insertions in this region are known to cause hereditary prion diseases.
• These diseases include Creutzfeldt-Jakob disease (CJD) and frontotemporal dementia.

Purpose of the Study:

• To investigate the role of 5-octapeptide repeat insertions (5-OPRI) in hereditary prion diseases.
• To determine the clinical presentation and diagnostic criteria associated with 5-OPRI.
• To evaluate 5-OPRI as a potential causative mutation for early-onset dementia.

Main Methods:

• Genetic analysis of affected individuals.
• Clinical case study review.
• Comparison with existing literature on PRNP mutations and prion diseases.

Main Results:

• A 5-octapeptide repeat insertion (5-OPRI) was identified in siblings with frontotemporal dementia.
• The identified 5-OPRI rarely met the diagnostic criteria for Creutzfeldt-Jakob disease (CJD).
• Findings align with previous research indicating 5-OPRI's association with dementia phenotypes.

Conclusions:

• 5-octapeptide repeat insertion (5-OPRI) is a suspected causative mutation for early-onset dementia.
• Frontotemporal dementia is a key phenotype associated with 5-OPRI.
• Further research is warranted to fully elucidate the pathogenic mechanisms of 5-OPRI.