The molecular basis of familial hypercholesterolaemia in Turkish patients


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

ATHEROSCLEROSIS, cilt.180, sa.1, ss.63-71, 2005 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 180 Konu: 1
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1016/j.atherosclerosis.2004.12.042
  • Dergi Adı: ATHEROSCLEROSIS
  • Sayfa Sayıları: ss.63-71

Özet

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.