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Familial Creutzfeldt-Jakob disease with a five-repeat octapeptide insert mutation
E J Cochran1, D A Bennett, L Cervenáková
1Department of Neurological Sciences, Rush Alzheimer's Disease Center, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, USA.
Neurology
|September 1, 1996
Summary
A novel PRNP gene mutation caused a rare familial form of Creutzfeldt-Jakob disease in a Ukrainian-American family, leading to varied symptoms and disease progression. This genetic prion disease highlights early onset and prolonged illness durations.
Area of Science:
- Neurology
- Genetics
- Prion Diseases
Background:
- Familial Creutzfeldt-Jakob disease (fCJD) is a rare, fatal neurodegenerative disorder.
- Genetic mutations in the prion protein gene (PRNP) are associated with fCJD.
- Previous insert mutations in PRNP have shown diverse clinical presentations.
Purpose of the Study:
- To characterize a unique PRNP gene insert mutation in an American family of Ukrainian origin with familial Creutzfeldt-Jakob disease.
- To investigate the clinical, genetic, and pathological features of this novel mutation.
Main Methods:
- Clinical evaluation of affected family members.
- Genetic analysis of the PRNP gene.
- Neuropathological examination of autopsy cases.
Main Results:
- Identified a novel PRNP gene insert mutation (five extra octapeptide repeats between codons 51-91) in ten affected family members.
- Observed early age of onset (proband at 42 years) and prolonged illness duration (up to 8 years).
- Documented significant clinical heterogeneity, including personality changes, cognitive impairment, spasticity, and variable pathological findings (spongiform change, neuronal loss, astrocytosis, or minimal abnormality).
Conclusions:
- This study reports a new PRNP gene insert mutation responsible for familial Creutzfeldt-Jakob disease.
- The findings confirm early onset, prolonged clinical course, and significant clinical and pathological heterogeneity associated with PRNP insert mutations.
- This mutation provides further insight into the genetic basis and phenotypic variability of prion diseases.