Abstract
Objective: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterised by defective cholesterol removal from the circulation and hypercholesterolemia caused by mutations in the low density lipoprotein receptor gene (LDLR). Although the definitive diagnosis is made by mutation analysis, some diagnostic criteria have been described due to the impracticality of routine mutation analysis. This study aims to compare the mutation status of familial hypercholesterolemia patients and their diagnosis according to the Simone-Broome criteria (SBC).Material and Methods: All patients with primary hyperlipidemia followed at the Metabolism and Nutrition Unit of Hacettepe University Faculty of Medicine were classified according to the Fredrickson classification system. Patients with type IIa hyperlipoproteinemia were assessed by SBC for the diagnosis of FH. Denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing were performed on the most frequently mutated exons (9 and 12). Mutation analyses of this and previous cohorts were compared with SBC in terms of diagnostic compatibility.Results: 118 of 163 patients with primary hyperlipidemia were type IIa hyperlipoproteinemia according to Fredrickson classification. According to the SBC, 48% of these patients were in the “probable FH”, 26% in the “definite FH”, and 17% in the “no FH” group, and 9% could not be classified due to lacking data. A heterozygous I420N (C.1322T>A) mutation on exon 9 was detected in 2 patients and a W556R (C.1729T>C) mutation on exon 12 was detected as heterozygous in one
and homozygous in one patient. Evaluation of mutation analysis results of patients with a mutation analysis including the 29 patients
who were previously analysed revealed, a mutation in 10 out of 10 patients (100%) in the definite FH, 12 out of 16 (75%) patients in the
probable FH and in 1 out of 3 (33%) patients in the no FH group.
Conclusion: The use of Simone-Broome criteria is a practical and reliable method in the diagnosis of familial hypercholesterolemia as routine
mutation screening is not a feasible choice and is usually performed in selected cases
Keywords: Child, Fredricson classification system, Genetic Screening, Hyperlipoproteinemia Type IIa, LDL Receptor, Simone-Broome criteria
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