TY - JOUR
T1 - Sporadic Creutzfeldt-Jakob Disease in a Woman Married Into a Gerstmann-Sträussler-Scheinker Family
T2 - An Investigation of Prions Transmission via Microchimerism
AU - Areškeviciute, Aušrine
AU - Melchior, Linea Cecilie
AU - Broholm, Helle
AU - Krarup, Lars-Henrik
AU - Lindquist, Suzanne Granhøj
AU - Johansen, Peter
AU - McKenzie, Neil
AU - Green, Alison
AU - Nielsen, Jørgen Erik
AU - Laursen, Henning
AU - Lund, Eva Løbner
PY - 2018/8/1
Y1 - 2018/8/1
N2 - This is the first report of presumed sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Str€aussler-Scheinker disease (GSS) with the prion protein gene c.305C>T mutation (p.P102L) occurring in one family. The father and son were affected with GSS and the mother had a rapidly progressive form of CJD. Diagnosis of genetic, variant, and iatrogenic CJD was ruled out based on the mother's clinical history, genetic tests, and biochemical investigations, all of which supported the diagnosis of sCJD. However, given the low incidence of sCJD and GSS, their co-occurrence in one family is extraordinary and challenging. Thus, a hypothesis for the transmission of infectious prion proteins (PrPSc) via microchimerism was proposed and investigated. DNA from 15 different brain regions and plasma samples of the CJD patient was subjected to PCR and shallow sequencing for detection of a male sex-determining chromosome Y (chr. Y). However, no trace of chr. Y was found. A long CJD incubation period or presumed small concentrations of chr. Y may explain the obtained results. Further studies of CJD and GSS animal models with controlled genetic and proteomic features are needed to determine whether maternal CJD triggered via microchimerism by a GSS fetus might present a new PrPSc transmission route.
AB - This is the first report of presumed sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Str€aussler-Scheinker disease (GSS) with the prion protein gene c.305C>T mutation (p.P102L) occurring in one family. The father and son were affected with GSS and the mother had a rapidly progressive form of CJD. Diagnosis of genetic, variant, and iatrogenic CJD was ruled out based on the mother's clinical history, genetic tests, and biochemical investigations, all of which supported the diagnosis of sCJD. However, given the low incidence of sCJD and GSS, their co-occurrence in one family is extraordinary and challenging. Thus, a hypothesis for the transmission of infectious prion proteins (PrPSc) via microchimerism was proposed and investigated. DNA from 15 different brain regions and plasma samples of the CJD patient was subjected to PCR and shallow sequencing for detection of a male sex-determining chromosome Y (chr. Y). However, no trace of chr. Y was found. A long CJD incubation period or presumed small concentrations of chr. Y may explain the obtained results. Further studies of CJD and GSS animal models with controlled genetic and proteomic features are needed to determine whether maternal CJD triggered via microchimerism by a GSS fetus might present a new PrPSc transmission route.
U2 - 10.1093/jnen/nly043
DO - 10.1093/jnen/nly043
M3 - Journal article
C2 - 29889261
SN - 0022-3069
VL - 77
SP - 673
EP - 684
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 8
ER -