TY - JOUR
T1 - Mutation of the prion protein in libyan jews with creutzfeldt–jakob disease
AU - Hsiao, Karen
AU - Meiner, Zeev
AU - Kahana, Esther
AU - Cass, Carin
AU - Kahana, Irit
AU - Avrahami, Dana
AU - Scarlato, Guglielmo
AU - Abramsky, Oded
AU - Prusiner, Stanley B.
AU - Gabizon, Ruth
PY - 1991/4/18
Y1 - 1991/4/18
N2 - Creutzfeldt—Jakob disease is a transmissible neurodegenerative disorder that occurs more than 100 times more frequently among Libyan Jews than in the worldwide population. We examined 11 patients with the disease — 10 Libyan Jews from Israel and 1 Libyan Jew from Italy — to determine whether abnormalities of the prion protein could be detected in them. Abnormal forms of this host-encoded protein are the predominant if not sole components of the transmissible agent that causes the disease. The prion-protein open-reading frame in peripheral-leukocyte DNA from the Italian patient was amplified with the polymerase chain reaction and sequenced. Allele-specific oligonucleotide hybridization was used to assess a prion-protein codon 200 lysine mutation in the 10 Israeli patients and 37 control subjects. The prion-protein sequence in DNA from the Italian patient revealed a single nucleotide change (G→A) at the first position of codon 200 that resulted in a substitution of lysine for glutamate. This substitution was detected in all 10 Israeli patients, 8 of whom had a positive family history of Creutzfeldt—Jakob disease. One patient was homozygous for the lysine mutation, and her clinical course did not differ from that of the patients heterozygous for the mutation. The lysine mutation was not found in one Moroccan Jew from Israel with Creutzfeldt—Jakob disease. The codon 200 lysine mutation of the prion-protein gene is consistently present among Libyan Jews with Creutzfeldt—Jakob disease, strongly supporting a genetic pathogenesis of their illness. The similarity of the clinical courses of the patient homozygous for this mutation and the patients heterozygous for it argues that familial Creutzfeldt—Jakob disease is a true dominant disorder.
AB - Creutzfeldt—Jakob disease is a transmissible neurodegenerative disorder that occurs more than 100 times more frequently among Libyan Jews than in the worldwide population. We examined 11 patients with the disease — 10 Libyan Jews from Israel and 1 Libyan Jew from Italy — to determine whether abnormalities of the prion protein could be detected in them. Abnormal forms of this host-encoded protein are the predominant if not sole components of the transmissible agent that causes the disease. The prion-protein open-reading frame in peripheral-leukocyte DNA from the Italian patient was amplified with the polymerase chain reaction and sequenced. Allele-specific oligonucleotide hybridization was used to assess a prion-protein codon 200 lysine mutation in the 10 Israeli patients and 37 control subjects. The prion-protein sequence in DNA from the Italian patient revealed a single nucleotide change (G→A) at the first position of codon 200 that resulted in a substitution of lysine for glutamate. This substitution was detected in all 10 Israeli patients, 8 of whom had a positive family history of Creutzfeldt—Jakob disease. One patient was homozygous for the lysine mutation, and her clinical course did not differ from that of the patients heterozygous for the mutation. The lysine mutation was not found in one Moroccan Jew from Israel with Creutzfeldt—Jakob disease. The codon 200 lysine mutation of the prion-protein gene is consistently present among Libyan Jews with Creutzfeldt—Jakob disease, strongly supporting a genetic pathogenesis of their illness. The similarity of the clinical courses of the patient homozygous for this mutation and the patients heterozygous for it argues that familial Creutzfeldt—Jakob disease is a true dominant disorder.
UR - http://www.scopus.com/inward/record.url?scp=0025869213&partnerID=8YFLogxK
U2 - 10.1056/NEJM199104183241604
DO - 10.1056/NEJM199104183241604
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C2 - 2008182
AN - SCOPUS:0025869213
SN - 0028-4793
VL - 324
SP - 1091
EP - 1097
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 16
ER -