Next-generation-sequencing-based identification of familial hypercholesterolemia-related mutations in subjects with increased LDL–C levels in a latvian population

• DOI: 10.1186/s12881-015-0230-x
• Publication Date: 2015-09-28T14:51:36Z
• Authors: Ilze Radovica-Spa...; Gustavs Latkovskis; Ivars Silamikelis; Davids Fridmanis; Ilze Elbere; Karlis Ventins; Guna Ozola; Andrejs Erglis; Janis Klovins
• Keywords: PCSK9; Nonsynonymous substitution

Familial hypercholesterolemia (FH) is one of the commonest monogenic disorders, predominantly inherited as an autosomal dominant trait. When untreated, it results in early coronary heart disease. The vast majority FH remains undiagnosed Latvia. identification and treatment affected individuals remain a challenge worldwide. Most cases are caused by mutations four genes, APOB, LDLR, PCSK9, or LDLRAP1. spectrum disease-causing variants very diverse variation detection panels usually used its diagnosis cover only minority gene variants. However, DNA-based tests may provide for patients with no physical symptoms known family history Here, we evaluate use targeted next-generation sequencing (NGS) to identify cohort artery disease (CAD) abnormal low-density lipoprotein–cholesterol (LDL–C) levels. We amplification coding regions LDLRAP1, followed NGS, 42 CAD (LDL–C, 4.1–7.2 mmol/L) 50 from population-based 5.1–9.7 mmol/L). In total, 22 synonymous 31 nonsynonymous variants, eight close proximity (10 bp) intron–exon boundaries, other were found. identified pathogenic (p.(Arg3527Gln) p.(Gly20Arg), p.(Arg350*), c.1706–10G > A LDLR) seven (7.6 %). Three possible also found patients. NGS-based methods can be detect high-risk when they do not meet defined clinical criteria.