Mutation and Polymorphism of the Prion Protein Gene in Libyan Jews
with Creutzfeldt-Jakob Disease (CJD)
R. Gabizon, H. Rosenman, Z. Meiner, I. Kahana, E. Kahana, Y. Shugart,
J. Ott, S.B. Prusiner
American Journal of Human Genetics , 53(4), 828--835 (1993 Oct)
Abstract
The inherited prion diseases are neurodegenerative disorders which
are not only genetic but also transmissible. More than a dozen
mutations in the prion protein gene that result in nonconservative
amino acid substitutions segregate with the inherited prion diseases
including familial Creutzfeldt-Jakob disease (CJD). In Israel, the
incidence of CJD is about 1 case/10(4) Libyan Jews. A Lys200
substitution segregates with CJD and is reported here to be
genetically linked to CJD with a lod score of > 4.8. Some healthy
elderly Lys200 carriers > age 65 years were identified, suggesting
the possibility of incomplete penetrance. In contrast, no linkage
was found between the development of familial CJD and a polymorphism
encoding either Met129 or Val129. All Libyan Jewish CJD patients
with the Lys200 mutation encode a Met129 on the mutant allele.
Homozygosity for Met129 did not correlate with age at disease onset
or the duration of illness. The frequency of the Met129 allele was
higher in the affected pedigrees than in a control population of
Libyan Jews. The frequency of the Met129 and Val129 alleles in the
control Libyan population was similar to that found in the general
Caucasian population. The identification of three Libyan Jews
homozygous for the Lys200 mutation suggests frequent intrafamilial
marriages, a custom documented by genealogical investigations.
