Rare E196A mutation in PRNP gene of 3 Chinese patients with Creutzfeldt-Jacob disease

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Inherited prion diseases represent a small but significant portion of human prion diseases, often linked to mutations in the prion protein gene (PRNP).
• Genetic Creutzfeldt-Jacob disease (gCJD) is a rare subtype requiring detailed case reports for understanding its diverse clinical and genetic landscape.

Observation:

• Three unrelated Han Chinese patients presented with clinical symptoms mimicking sporadic CJD, despite lacking a family history.
• Diagnostic evaluations revealed positive 14-3-3 proteins in cerebrospinal fluid and characteristic MRI abnormalities in all three cases.
• Two patients exhibited psychotic symptoms during their disease course, adding to the clinical variability.

Findings:

• A rare mutation in the PRNP gene, specifically an E196A substitution, was identified in all three unrelated gCJD patients.
• All patients were homozygotes for methionine at PRNP codon 129 and glutamate at codon 219.
• Disease duration ranged from 10 to 22 months, with varied initial and progressing clinical manifestations.

Implications:

• This report highlights the E196A PRNP mutation as a cause of gCJD in the Han Chinese population.
• The findings underscore the importance of genetic screening in diagnosing CJD, even in the absence of a family history.
• Understanding this rare mutation contributes to the broader knowledge of prion protein conformational changes and disease pathogenesis.