title: A novel point mutation in a splice acceptor site of intron 1 of the human low density lipoprotein receptor gene which causes severe hypercholesterolemia: an unexpected absence of exon skipping. Mutations in brief no. 139. Online.
abstract: Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in the low density lipoprotein (LDL)-receptor gene. We found a new mutation in the splice acceptor site of intron 1 of the LDL receptor gene, which is designated as 68-1 G->C according to the nomenclature suggested by Beaudet and Tsui (1993), in a Japanese FH homozygote. She was born from consanguineous marriage and has this mutation as a true homozygous form. Her cultured fibroblasts showed no LDL receptor protein synthesis. This mutation caused activation of a cryptic splice acceptor side in the downstream exon 2, leading to frameshift and appearance of premature in-frame stop codon. The mutation was detected by Dde I restriction enzyme. The identical mutation was not found among 24 patients with homozygous and 120 patients with heterozygous FH. The mutation was very rare among the Japanese population.
authors: Department of Etiology and Pathophysiology, National Cardiovascular Center Research Insitute, Osaka, Japan.
authors: T
authors: T
authors: Maruyama
authors: Y
authors: Y
authors: Miyake
authors: T
authors: T
authors: Yamamura
authors: S
authors: S
authors: Tajima
authors: T
authors: T
authors: Funahashi
authors: Y
authors: Y
authors: Matsuzawa
authors: A
authors: A
authors: Yamamoto
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D007438:Introns / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL