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The molecular basis of familial hypercholesterolaemia in Turkish patients.
63 - 71.
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.
|Title:||The molecular basis of familial hypercholesterolaemia in Turkish patients.|
|Keywords:||Adolescent, Child, Child, Preschool, Frameshift Mutation, Gene Deletion, Genetic Heterogeneity, Genetic Testing, Humans, Hyperlipoproteinemia Type II, Polymorphism, Single-Stranded Conformational, Receptors, LDL, Turkey|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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