The molecular basis of familial hypercholesterolaemia in Turkish patients

Atherosclerosis. 2005 May;180(1):63-71. doi: 10.1016/j.atherosclerosis.2004.12.042.

Abstract

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipoprotein metabolism. In the majority of patients FH is caused by mutations in the gene for the low-density lipoprotein receptor (LDLR), and to date more than 700 mutations have been reported worldwide. In this study, 36 paediatric patients with a clinical diagnosis of FH (20 homozygous and 16 heterozygotes) were screened for mutations in the LDLR gene. Each exon, with intron-exon junctions, was screened by capillary fluorescent SSCP (F-SSCP) and heteroduplex analysis. Samples showing different band patterns were sequenced. Ten novel (including three frame shift small deletions or insertions) and seven known mutations were detected. A total of 37 out of the predicted 56 FH-causing alleles were identified (66.1%). No patients with the R3500Q mutation in the APOB gene were found. W556R was the most common mutation, explaining 21.4% of the predicted defective LDLR alleles. The novel sequence changes were deemed to be pathogenic if they altered a conserved amino acid (L143P, D147E, Q233H-C234G, C347G) or occurred in or close to a splice site (IVS 16+5) and were absent in DNA from 50 healthy Turkish subjects. These data confirm the genetic heterogeneity of FH in Turkey, and demonstrate the usefulness of F-SSCP for mutation detection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Frameshift Mutation
  • Gene Deletion
  • Genetic Heterogeneity
  • Genetic Testing
  • Humans
  • Hyperlipoproteinemia Type II / genetics*
  • Polymorphism, Single-Stranded Conformational*
  • Receptors, LDL / genetics*
  • Turkey

Substances

  • Receptors, LDL