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Creutzfeldt‐Jakob disease cosegregates with the codon 178 Asn PRNP mutation in families of European origin
Author(s) -
Goldfarb Lev G.,
Brown Paul,
Haltia Matti,
Cathala Françoise,
McCombie W. Richard,
Kovanen Jussi,
Červen̆áková Larisa,
Goldin Lynn,
Nieto Ana,
Godec Mark S.,
Asher David M.,
Gajdusek D. Carleton
Publication year - 1992
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410310308
Subject(s) - prnp , mutation , genetics , disease , biology , gene , genotype , medicine
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 occurence 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, patietns 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 178 Asn is the actual disease mutation.