title: An insert mutation in the chromosome 20 amyloid precursor gene in a Gerstmann-Sträussler-Scheinker family.
abstract: We report the finding of an insert mutation in the chromosome 20 amyloid precursor gene in a family with neuropathologically-verified, experimentally-transmitted Gerstmann-Sträussler-Scheinker syndrome (GSS). The insert consisted of 8 extra copies of a repeating octapeptide coding sequence in the region between codons 51 and 91; it was identified in the proband and a presently unaffected at-risk niece by full sequencing of the open reading frame, and was visualized electrophoretically in the proband and 6 of 12 at-risk relatives. Although affected members in this French-Breton family have shown a variety of clinical profiles, including durations of illness that ranged from 3 months to 13 years, all autopsied cases (including the patient with the shortest illness) have had the distinctive multicentric amyloid plaques that define GSS as a nosologic entity.
authors.affiliation: Laboratory of CNS Studies, NINDS, NIH, Bethesda, MD 20892.
authors.forename: L G
authors.initials: LG
authors.lastname: Goldfarb
authors.forename: P
authors.initials: P
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Vrbovská
authors.forename: H
authors.initials: H
authors.lastname: Baron
authors.forename: W R
authors.initials: WR
authors.lastname: McCombie
authors.forename: F
authors.initials: F
authors.lastname: Cathala
authors.forename: C J
authors.initials: CJ
authors.lastname: Gibbs
authors.forename: D C
authors.initials: DC
authors.lastname: Gajdusek
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016380:Brain Tissue Transplantation / Q000009:adverse effects; D002890:Chromosomes, Human, Pair 20; D003062:Codon; D005260:Female; D016098:Gerstmann-Straussler-Scheinker Disease / Q000235:genetics* / Q000635:transmission; D000882:Haplorhini; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D002679:Pan troglodytes; D010375:Pedigree; D014183:Transplantation, Heterologous
chemical_list: D016564:Amyloid beta-Protein Precursor; D003062:Codon