Novel Prion Disease Identified Involving Mutation in PRNP
(HealthDay News) – A novel prion disease with a truncation mutation in the gene encoding prion protein (PRNP) has been identified, according to a study published in the Nov. 14 issue of the New England Journal of Medicine.
Simon Mead, MD, from University College London, and colleagues characterized a novel prion disease in a large British kindred using longitudinal clinical assessments over a 20-year period, combined with genealogical, neuropsychological, neurophysiological, neuroimaging, pathological, molecular genetic, and biochemical studies. Six of the 11 affected family members were studied in detail, and autopsy or biopsy samples were investigated from five family members.
The researchers identified a PRNP Y163X truncation mutation. A distinct and consistent phenotype of chronic diarrhea with autonomic failure was described, together with a length-dependent axonal, mainly sensory, peripheral polyneuropathy, with early adulthood onset. When patients were in their 40s or 50s, cognitive decline and seizures occurred. Throughout the peripheral organs, the deposition of prion protein amyloid was observed, including in the bowel and peripheral nerves. During end-stage disease, neuropathological examination showed the deposition of prion protein in the form of frequent cortical amyloid plaques, cerebral amyloid angiopathy, and tauopathy. In brain tissue, a unique pattern of abnormal prion protein fragments was seen. In laboratory mice, transmission studies were negative.
"Abnormal forms of prion protein that were found in multiple peripheral tissues were associated with diarrhea, autonomic failure, and neuropathy," the authors write.
Two authors disclosed financial ties to the pharmaceutical industry; two authors disclosed financial ties to D-Gen Limited, which commercializes research from the field of prion disease.