The molecular basis of familial hypercholesterolaemia in Turkish patients

SÖZEN M. M. , Whittall R., Oner C., Tokatli A., Kalkanoglu H., Dursun A., ...More

ATHEROSCLEROSIS, vol.180, no.1, pp.63-71, 2005 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 180 Issue: 1
  • Publication Date: 2005
  • Doi Number: 10.1016/j.atherosclerosis.2004.12.042
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.63-71
  • Keywords: familial hypercholesterolaemia, FH, LDLR, SSCP, Turkish, mutation screening, LDL-RECEPTOR GENE, APOLIPOPROTEIN-B, MUTATION, IDENTIFICATION, SPECTRUM, LOCUS
  • Hacettepe University Affiliated: Yes


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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.