Creutzfeldt-Jakob disease cosegregates with the codon 178Asn PRNP mutation in families of European origin.
We recently discovered an amino acid-altering heterozygous mutation in codon 178 of the PRNP amyloid precursor gene in patients with familial Creutzfeldt-Jakob disease. This mutation is now shown to be associated with the occurrence of disease in 7 unrelated families of Western European origin, among which a total of 65 members are known to have died from Creutzfeldt-Jakob disease. The mutation was detected in each of 17 tested patients, including at least 1 affected member of each family, and in 16 of 36 of their first-degree relatives, but not in affected families with other mutations, patients with the nonfamilial form of the disease, or 83 healthy control individuals. Linkage analysis in two informative families yielded a lod score of 5.30, which, because no recombinants were found, strongly suggests that codon 178Asn is the actual disease mutation.
Goldfarb
L G
LG
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Brown
P
P
Haltia
M
M
Cathala
F
F
McCombie
W R
WR
Kovanen
J
J
Cervenáková
L
L
Goldin
L
L
Nieto
A
A
Godec
M S
MS
D000328:Adult; D001483:Base Sequence; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005060:Europe / Q000208:ethnology; D005260:Female; D005796:Genes; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D007729:Kuru / Q000235:genetics; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018621:PrPC Proteins; D011328:Prions / Q000235:genetics* / Q000648:ultrastructure; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics* / Q000648:ultrastructure
D003062:Codon; D018621:PrPC Proteins; D011328:Prions; D011498:Protein Precursors