title: A novel splice site mutation of the LDL receptor gene in a Tunisian hypercholesterolemic family.
abstract: BACKGROUND
  Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by mutations in either the low-density lipoprotein receptor, the apolipoprotein B or the proprotein convertase subtilisin/kexin type 9 genes. It is characterized by a high concentration of low-density lipoprotein (LDL), which frequently gives rise to premature coronary disease. In this study, we report a novel splice site mutation of the LDL receptor gene in a Tunisian family.
  
  
  METHODS
  Seven patients from the family were screened for mutations in the LDLR gene and the apoB gene, using direct sequencing. RT-PCR and study on cultured skin fibroblast were realised to characterize the effect of novel mutation.
  
  
  RESULTS
  Direct sequencing of the promoter and 18 exons reveals a G>A substitution in the splice site junction of intron 8 (c.1186+1 G>A). Study on cultured skin fibroblasts showed a residual activity of 10% of the LDL receptor. Reverse transcription, amplification and direct sequencing of RNA from patient's lymphocytes reveal a deletion of the final 51 bp of exon 8 preserving the reading frame.
  
  
  CONCLUSIONS
  The study identified a novel splice mutation c.1186+1 G>A in the LDL receptor gene. It causes the utilization of a new cryptic donor splice site 51 bp downstream from the normal site.
authors: Research Unit of Genetic and Biologic Factors of Atherosclerosis, Faculty of Medecine, Monastir, Tunisia.
authors: A
authors: A
authors: Jelassi
authors: M
authors: M
authors: Najah
authors: I
authors: I
authors: Jguirim
authors: F
authors: F
authors: Maatouk
authors: S
authors: S
authors: Lestavel
authors: O S
authors: OS
authors: Laroussi
authors: M
authors: M
authors: Rouis
authors: C
authors: C
authors: Boileau
authors: J P
authors: JP
authors: Rabès
authors: M
authors: M
authors: Varret
authors: M N
authors: MN
authors: Slimane
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005190:Family; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics*; D007438:Introns; D008297:Male; D008875:Middle Aged; D009154:Mutation; D022821:RNA Splice Sites; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D014416:Tunisia
chemical_list: D001055:Apolipoproteins B; D022821:RNA Splice Sites; D011973:Receptors, LDL