Systematic prediction of familial hypercholesterolemia caused by low-density lipoprotein receptor missense mutations

摘要

Background and aims: Familial hypercholesterolemia (FH) is a an autosomal dominant disorder characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). It is estimated that 85% of all FH-causing mutations involve genetic variants in the LDL receptor (LDLR). To date, 795 single amino acid LDLR missense mutations have been reported in the Leiden Open Variation Database (LOVD). However, the functional impact of these variants on the LDLR pathway has received little attention and remains poorly understood. We aim to establish a systematic functional prediction model for LDLR single missense mutations.