title: Mutation analysis of the chromosome 14q24.3 dihydrolipoyl succinyltransferase (DLST) gene in patients with early-onset Alzheimer disease.
abstract: Linkage analysis studies have indicated that the chromosome band 14q24.3 harbours a major gene for familial early-onset Alzheimer's disease (AD). Recently we localized the chromosome 14 AD gene (AD3) in the 6.4 cM interval between the markers D14S289 and D14S61. We mapped the gene encoding dihydrolipoyl succinyltransferase (DLST), the E2k component of human alpha-ketoglutarate dehydrogenase complex (KGDHC), in the AD3 candidate region using yeast artificial chromosomes (YACs). The DLST gene is a candidate for the AD3 gene since deficiencies in KGDHC activity have been observed in brain tissue and fibroblasts of AD patients. The 15 exons and the promoter region of the DLST gene were analysed for mutations in chromosome 14 linked AD cases and in two series of unrelated early-onset AD cases (onset age < 55 years). Sequence variations in intronic sequences (introns 3, 5 and 10) or silent mutations in exonic sequences (exons 8 and 14) were identified. However, no AD related mutations were observed, suggesting that the DLST gene is not the chromosome 14 AD3 gene.
authors.affiliation: Born-Bunge Foundation, University of Antwerp (UIA), Department of Biochemistry, Antwerpen, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Cruts
authors.forename: H
authors.initials: H
authors.lastname: Backhovens
authors.forename: G
authors.initials: G
authors.lastname: Van Gassen
authors.forename: J
authors.initials: J
authors.lastname: Theuns
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Wehnert
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: T
authors.initials: T
authors.lastname: Karlsson
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: R
authors.initials: R
authors.lastname: Adolfsson
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005091:Exons; D008040:Genetic Linkage; D006801:Humans; D007438:Introns; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic
chemical_list: D000217:Acyltransferases; C021515:dihydrolipoamide succinyltransferase