20.500.12556/DiRROS-28854 Cascade screening of a Pakistani consanguineous familial hypercholesterolemia cohort identification of seven new homozygous patients Background and aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, significantly increasing the risk of premature cardiac events and mortality. In Pakistan, despite the potential burden of FH, comprehensive studies evaluating its genetic characteristics, cascade screening significance, and lipoprotein (a) [Lp(a)] levels remain scarce. Understanding these factors is crucial for effective diagnosis, risk assessment, and management of FH in the Pakistani population. Methods: After the identification of index case with clinical homozygous FH, characterized by high LDL-C and high Lp(a) levels together with a positive personal and family history of cardiovascular disease, a cascade screening of 66 relatives from a consanguineous family was performed. Blood samples were obtained from all subjects for biochemical and genetic analysis. Simon Broome criteria was applied on children for clinical FH diagnosis. Dutch Lipid Clinic Network scores were calculated for individuals aged ≥16years. Genetic screening was performed using next-generation sequencing to analyse all coding regions and exon-intron borders of the following genes: ALMS1, APOA1, APOB, APOA5, APOC2, APOC3, APOE, ABCA1, ABCG5, ABCG8, CREB3L3, GPIHBP1, LDLR, LDLRAP1, LIPA, LMF1, LPL, and PCSK9. The identified variants were confirmed using Sanger sequencing. Results: Cascade screening identified seven homozygous and 25 heterozygous FH patients with pathogenic variant in the LDLR gene (NM_000527.5: c.2416dupG: p. Val806GlyfsTer11). Additionally, heterozygous variants of uncertain significance were identified in 4 other subjects. Conclusion: This study underscores the high effectiveness of cascade screening in consanguineous families and societies that could lead to early detection and prevention. cardiovascular disease cascade screening consanguineous familial hypercholesterolemia homozygous kaskadno presejanje krvno sorodstvo družinska hiperholesterolemija homozigot true false true Angleški jezik Slovenski jezik Neznano 2026-04-09 13:19:11 2026-04-09 13:19:11 2026-04-10 03:55:40 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 7. 3. 2025; str. 1-7 Vol. 402, [article no.] 119118 Feb 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.4-053.2 1879-1484 10.1016/j.atherosclerosis.2025.119118 228355075 RAZ_Ain_Quratul_2025.pdf RAZ_Ain_Quratul_2025.pdf 1 3C516D213FFC4DCC33F1F14F37D6739B 9e9d9cd1633b4db88fa4355cffdfe041394364da05c17f72fd98c33dce5fa30d 5913976a-3406-11f1-b941-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43004 https://www.atherosclerosis-journal.com/article/S0021-9150(25)00015-2/fulltext 1 f1b06b1a-3405-11f1-b941-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43003 Univerzitetni klinični center Ljubljana 0 0 0