Evaluation Of Massive Parallel Sequencing As A Diagnostic Tool For Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) was first described in 1920 (Burns, 1920). It affects about one in 500 individuals (Graham et al., 2005). FH is the most common single gene disorder and is mostly inherited as an autosomal dominant trait. The physical sign of FH is tendon xantomas, but these are not present in every family (Graham et al., 1999). Identification and early treatment of affected individuals is desirable and in lack of physical symptoms DNA-based diagnosis provides confirmation of diagnosis and enables early patient management (Graham et al., 2005). In the majority of FH cases individuals have defective low density lipoprotein receptor (LDLR) which leads to accumulation of low density lipoprotein cholesterol (LDL-C) in plasma (Graham et al., 2005; Humphries et al., 2006b). Raised cholesterol concentrations in the blood are present from birth and lead to early development of atherosclerosis and coronary heart disease (DeMott, 2008). About half of men with FH will develop coronary heart disease by the age of 55. FH-affected women typically develop coronary heart disease about nine years later than men (Slack, 1969). The proportion of patients with FH identified and being treated is quite low, with most of these being young people (Humphries et al., 2006b). PROCEEDINGS OF THE LATVIAN ACADEMY OF SCIENCES. Section B DOI: 10.2478/prolas-2014-0011