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Updated: Nov 14, 2025
Protein Misfolding Cyclic Amplification of Prions
Published on: November 7, 2012
Genetic prion disease: D178N with 129MV disease modifying polymorphism-a clinical phenotype
Tracie Huey-Lin Tan1, Richard J Stark1,2, John A Waterston1
1Neurology, Alfred Health, Melbourne, Victoria, Australia.
Background:
Human prion diseases are a group of rare neurological diseases with a minority due to genetic mutations in the prion protein (PRNP) gene. The D178N mutation is associated with both Creutzfeldt-Jakob disease and fatal familial insomnia with the phenotype modified by a polymorphism at codon 129 with the methionine/valine (MV) polymorphism associated with atypical presentations leading to diagnostic difficulty.
Case:
We present a case of fatal familial insomnia secondary to a PRNP D178N mutation with 129MV disease modifying polymorphism who had no family history, normal MRI, electroencephalography (EEG), cerebrospinal fluid (CSF) and positron emission tomography findings and a negative real-time quaking-induced conversion result.
Conclusion:
Patients with genetic prion disease may have no known family history and normal EEG, MRI brain and CSF findings. PRNP gene testing should be considered for patients with subacute progressive neurological and autonomic dysfunction.
Insights
Genetic prion diseases, like fatal familial insomnia, can present atypically without family history or abnormal standard tests. PRNP gene testing is crucial for diagnosing unexplained neurological and autonomic dysfunction.
Area of Science:
- Neurology
- Genetics
- Molecular Biology
Background:
- Human prion diseases are rare neurological disorders.
- A subset is caused by mutations in the prion protein (PRNP) gene.
- The PRNP D178N mutation is linked to Creutzfeldt-Jakob disease and fatal familial insomnia, with the 129MV polymorphism influencing atypical presentations.
Purpose of the Study:
- To report a case of fatal familial insomnia (FFI) due to a PRNP D178N mutation.
- To highlight diagnostic challenges in genetic prion diseases.
- To emphasize the importance of PRNP gene testing in specific clinical scenarios.
Main Methods:
- Case presentation of FFI.
- Genetic analysis for PRNP mutations.
- Standard neurological diagnostic workup including MRI, EEG, CSF analysis, and PET scans.
- Real-time quaking-induced conversion (RT-QuIC) assay.
Main Results:
- The patient had a PRNP D178N mutation with the 129MV polymorphism.
- The patient lacked a family history of prion disease.
- Initial diagnostic tests (MRI, EEG, CSF, PET) and RT-QuIC were negative.
- The presentation was atypical, leading to diagnostic difficulty.
Conclusions:
- Genetic prion disease can occur without a known family history.
- Normal EEG, MRI, and CSF findings do not exclude genetic prion disease.
- PRNP gene testing is recommended for patients with subacute progressive neurological and autonomic dysfunction.
