Alves, Ana CatarinaBenito-Vicente, AsierMedeiros, Ana MargaridaReeves, KaajalMartin, CesarBourbon, Mafalda2018-10-182018-10-182018-10Atherosclerosis. 2018 Oct;277:448-456. doi: 10.1016/j.atherosclerosis.2018.06.819.0021-9150http://hdl.handle.net/10400.18/5622APOB mutations are a rare cause of familial hypercholesterolaemia (FH) and, until recently, routine genetic diagnosis only included the study of two small APOB fragments. In previous years, 5 novel functional mutations have been described in APOB fragments not routinely studied, our group having functionally characterized 2 of them. The main aim of this work was to identify and characterize novel alterations in APOB to assess the genetic cause of hypercholesterolemia in patients with a clinical diagnosis of FH.Highlights: The spectrum of functional alterations in APOB outside the fragments routinely screened is growing; We characterized two rare novel variants in APOB, p.(Thr3826Met) is pathogenic and p.(Pro994Leu) is neutral; The study of all 29 exons of APOB should be performed in routine diagnosis, now possible by NGS, since it is expected that a further 5–10% of clinical FH patients can have FH due to a novel APOB mutation; Due to low penetrance of APOB variants and high rate of common variants inAPOB, all novel variants need to be functionally characterized to prove their pathogenicity.engAPOB VariantsFamilial HypercholesterolemiaFunctional StudiesDoenças Cardio e Cérebro-vascularesjournal article10.1016/j.atherosclerosis.2018.06.819