| Abstract [eng] |
Although familial hypercholesterolaemia is a common congenital cause of elevated low-density lipoprotein cholesterol, it remains underdiagnosed and undertreated worldwide due to its genetic heterogeneity. Aim: To determine the prevalence of genetic mutations in patients with clinically suspected familial hypercholesterolaemia and to analyse the association between mutation pathogenicity and hypercholesterolaemia, early onset coronary artery disease and Dutch Lipid Clinic Network criteria. Methods: Anonymized data of 154 patients was used for retrospective analysis. The study included men and women aged 0-85 years with low density lipoprotein cholesterol concentrations greater than 4.9 mmol/l (adults) and >3.9 mmol/l (children). Results: 30.57% of subjects had mutations in LDLR, 14.65% in APOB and 0.64% in LDLRAP1 genes. The study identified 23 pathogenic mutation variants in genes associated with familial hypercholesterolemia. The most common mutations were LDLR c.654_656del p. (Gly219del) and APOB c.10580G>A p. (Arg3527Gln), which are associated with the founder effect. Carriers of likely pathogenic mutation variants and variants of uncertain significance have higher mean low-density lipoprotein cholesterol concentrations compared to the general population. There was a slight association between premature coronary artery disease and a higher Dutch Lipid Clinic Network criteria score. After genetic testing the number of patients classified as "Definite familial hypercholesterolaemia" increased by more than 70%. Conclusions: The variety of mutation variants detected, unveils the genetic polymorphism of this condition, and thus emphasises the need for further studies in different populations to elucidate the exact genetic basis of familial hypercholesterolemia. |
