Effects of a 9.6-kb deletion of the LDL receptor gene (FH Helsinki) on structure and levels of mRNA

Hum Mutat. 1998;12(2):95-102. doi: 10.1002/(SICI)1098-1004(1998)12:2<95::AID-HUMU4>3.0.CO;2-E.


FH Helsinki is a deletion of the low-density lipoprotein receptor (LDLR) gene that deletes 9.6 kb from intron 15 to exon 18. Screening for mutant transcripts by Northern blot analysis from a patient heterozygous for FH Helsinki revealed two mutant transcripts. One was a transcript where the proximal part of intron 15 was retained in mRNA. The second was a transcript where exon 15 was spliced to nucleotide 4186 of exon 18. Thus, this transcript was generated using the normal donor splice site in intron 15, and a cryptic AG acceptor splice site in exon 18. Translation of the two mutant transcripts is predicted to give nonfunctional proteins, as both the membrane-spanning domain and the cytoplasmic domain of the receptor are deleted. Scanning of the autoradiograms showed that the amounts of each of the two mutant transcripts were approximately 10 times higher than that of the normal transcript in our heterozygous patient. The finding of higher levels of mutant transcripts was confirmed by an allele-specific transcript quantitation method, in which the amount of the two mutant transcripts together was approximately 5 times higher than the amount of the normal transcript. Deletion of destabilizing elements (AU-rich elements) by FH Helsinki are proposed to cause the increased levels of mutant transcripts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Cells, Cultured
  • Female
  • Fibroblasts
  • Founder Effect
  • Genes, Dominant
  • Humans
  • Hyperlipoproteinemia Type II / genetics*
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Receptors, LDL / genetics*
  • Sequence Analysis, DNA
  • Sequence Deletion*


  • RNA, Messenger
  • Receptors, LDL