Exome sequencing reveals novel functional mutations in APOB causing Familial Hypercholesterolaemia

Introduction: Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Loss of function mutations in LDLR and APOB and also gain of function mutations in PCSK9 have been associated with FH, but mutations in LDLR are the most common cause of FH. Until 2012 only mutations in two small fragments of exon 26 and 29 were described as causing FH. In the last 2 years functional mutations in other fragments of exon 26 and 29 as well as in exon 3 and 22 have been reported in FH patients. However with Next Generation Sequencing techniques others alterations in fragments not studied in routine diagnosis are being found and need to be functional characterized. The main aim of this project was to characterize 2 novel alterations in APOB, exon 19 and 26, in order to identify the genetic cause of the hypercholesterolemia in these patients.FCT_PTDC/SAU-GMG/101874/2008; Ana Catarina Alves was funded by FCT SFRH / BD / 27990 / 2006 and FCT_PTDC/SAU-GMG/101874/200