Further evidence of novel APOB mutations as a cause of familial hypercholesterolaemia

Alves, Ana Catarina; Benito-Vicente, Asier; Medeiros, Ana Margarida; Reeves, Kaajal; Martin, Cesar; Bourbon, Mafalda

http://hdl.handle.net/10400.18/5622

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Authors

Alves, Ana Catarina

Benito-Vicente, Asier

Medeiros, Ana Margarida

Reeves, Kaajal

Martin, Cesar

Bourbon, Mafalda

Abstract(s)

APOB 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.