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

Eur J Biochem. 1995 Sep 15;232(3):700-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Base Sequence
  • Child, Preschool
  • DNA Primers / chemistry
  • Exons
  • Female
  • Fibroblasts
  • Homozygote
  • Humans
  • Hypercholesterolemia / genetics*
  • Introns
  • Molecular Sequence Data
  • Point Mutation*
  • Polymerase Chain Reaction
  • Receptors, LDL / chemistry
  • Receptors, LDL / genetics*
  • Restriction Mapping
  • Transcription, Genetic*

Substances

  • DNA Primers
  • Receptors, LDL