title: A single point mutation in the splice donor site of the low-density-lipoprotein-receptor gene produces intron read-through, exon-skipped and cryptic-site-utilized transcripts.
abstract: Familial hypercholesterolemia is a genetic disorder caused by mutations of the low-density-lipoprotein (LDL) receptor gene. We characterized the structures of LDL receptor mRNA transcripts in the fibroblasts of a homozygous patient carrying a single base substitution (T-->C) at the 5' splice donor site of intron 12 of the LDL receptor gene. We identified three aberrant transcripts as a consequence of intron-12 read-through, exon-12 skipping and utilization of a cryptic splice donor site. Only a point mutation at the 5' splice donor site caused the production of three alternatively spliced products. None of these transcripts produced a functional LDL receptor protein in this patient.
authors.affiliation: Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
authors.forename: S
authors.initials: S
authors.lastname: Tajima
authors.forename: T
authors.initials: T
authors.lastname: Funahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005260:Female; D005347:Fibroblasts; D006720:Homozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics*; D015183:Restriction Mapping; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D011973:Receptors, LDL