TY - JOUR T1 - A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia TT - JF - انستیتو-پاستور-ایران JO - انستیتو-پاستور-ایران VL - 25 IS - 5 UR - http://ibj.pasteur.ac.ir/article-1-3251-en.html Y1 - 2021 SP - 374 EP - 379 KW - Genetic research KW - LDLRAP1 KW - Hypercholesterolemia KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors N2 - Background: familial hypercholesterolemia (FH), a hereditary disorder, is caused by pathogenic variants in the LDLR, APOB, and PCSK9 genes. This study has assessed genetic variants in a family, clinically diagnosed with FH. Methods: A family was recruited from MASHAD study in Iran with possible FH based on the Simon Broom criteria. The DNA sample of an affected individual (proband) was analyzed using whole exome sequencing, followed by bioinformatics and segregation analyses. Results: A novel splice site variant (c.345-2A>G) was detected in the LDLRAP1 gene, which was segregated in all affected family members. Moreover, HMGCR rs3846662 g.23092A>G was found to be homozygous (G/G) in the proband, probably leading to reduced response to simvastatin and pravastatin. Conclusion: LDLRAP1 c.345-2A>G could alter the phosphotyrosine-binding domain, which acts as an important part of biological pathways related to lipid metabolism. M3 10.52547/ibj.25.5.374 ER -