Predominant spastic paraparesis associated with the D178N mutation in PRNP
Data files
Jun 02, 2021 version files 163.82 KB
-
Supplementary_document_210503.pdf
98.54 KB
-
Table_e-1_CSF_analyses.pdf
65.28 KB
Jul 28, 2021 version files 65.28 KB
-
Table_e-1_CSF_analyses.pdf
65.28 KB
Sep 26, 2021 version files 172.58 KB
-
Supplementary_document_final_version.pdf
107.30 KB
-
Table_e-1_CSF_analyses.pdf
65.28 KB
Abstract
Here we report on a 70-year-old female presenting with an unusual progressive syndrome with fatal outcome. The predominant features in this case were spastic paraparesis, cognitive decline and respiratory failure. Relatives affected with a similar syndrome were previously diagnosed with lipofuscinosis. However, whole-genome sequencing (WGS) in our case did not reveal any pathogenic variants in genes associated with lipofuscinosis, but instead detected the known D178 variant in PRNP. The course of disease was rapid despite the presence of methione at codon 129 in the mutated and valine in the healthy allele of PRNP. Typical neuropathological abnormalities for familial fatal insomnia (FFI) were found, Western blot analysis suggested a type 2B prion protein isoform. The serendipitous diagnosis obtained with WGS illustrates a role for the method in elusive cases.