Clinical and biochemical characteristics are varied in subjects with ABCA1 mutations

s / Atherosclerosis 241 (2015) e32ee71 e37 other fragments of exon 26 and 29 as well as in exon 3 and 22 have been reported in FH patients. The main aim of this project was to functional characterize novel alterations in exon 19 and 26 (APOB) found in clinical FH patients. Methods: LDL from 2 index patients and relatives was separated and marked with FITC-LDL to perform functional studies by flow cytometry with lymphocytes and HepG2, and U937 growth assays. Alterations were screened in a 96 normolipidaemic panel by PCR and sanger sequencing. Results: In vitro analysis of these variants showed a decrease in the binding and internalization of LDL and in U937 growth from individuals with exon 26 alteration, showing a similar effect as APO3527. As reported before also in this family the penetrance is also reduced. Alteration in exon 19 had a neutral effect. Both alterations were not present in the normolipidaemic panel. Conclusions: The spectrum of functional alterations in APOB outside the fragments routinely screened is growing. Screening of all 29 exons of APOB should be performed in routine diagnosis, now possible by NGS, since it is expected that a further 10% of clinical FH patients can have FH due to a novel APOB mutation. If so mutations in APOB can be a common cause of FH than expected. EAS-0599. CLINICAL AND BIOCHEMICAL CHARACTERISTICS ARE VARIED IN SUBJECTS WITH ABCA1 MUTATIONS M. Cuchel , J.T. McParland , J. Wang , R.A. Hegele , D.J. Rader . Department of Medicine Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, USA; Vascular Biology Research Group, Robarts Research Institute, London, Canada Aim: The ATP-binding cassette transporter 1 (ABCA1) is a membrane protein responsible for generating HDL through its ability to efflux phospholipid and cholesterol and for maintaining cellular cholesterol homeostasis. Recent data suggest that ABCA1 may affect other metabolic pathways beyond HDL metabolism. The clinical and biochemical characterization of subjects carrying mutations in the gene encoding for ABCA1 may help gain some insights into the frequency and pathophysiology of this condition. Methods: We performed a detailed lipid profile and ABCA1 sequencing in subjects with primary hypoalphalipoproteinemia. Where possible, family members of subjects carrying ABCA1 mutations were also studied. Results: ABCA1 mutations were found in 25 of 49 probands sequenced. Additional carriers were found among family members. Homozygous or compound heterozygous subjects (n1⁄413, age 30±12 years) had HDL-cholesterol1⁄46.5±8.0 mg/dl (median 4, range 1-31 mg/dl) and mean apoA-I1⁄4 21±31 mg/dl. Of these 13 subjects, 3 (23%) had enlarged tonsils, 2 (15%) reported neuropathy, 1 (8%) had clinically evident CAD, and none had diabetes. Heterozygous subjects (n1⁄431, age 39±18 years) had HDL-cholesterol1⁄422±9 mg/dl and apoA-I1⁄4 80±37 mg/dl. Of these, 4 (13%) had diabetes, and 2 (6%) had clinically evident CAD. Conclusions: ABCA1mutations may be amore common cause of lowHDLcholesterol than is appreciated. Additionally, these data highlight the broad spectrum of HDL-cholesterol and apoA-I levels as well as clinical characteristics that are found in carriers of ABCA1 mutations. EAS-0660. THE CARDIOVASCULAR GENE ANNOTATION INITIATIVE: IMPACT ON DATA ANALYSIS R.C. Lovering , M. Rodriguez-Lopez , N.H. Campbell , R.P. Huntley , T. Sawford , C. O’Donovan , S. Orchard , H. Hermjakob , M. Martin , M. Mayr , S.E. Humphries , P.J. Talmud . 1 Institute of Cardiovascular Science, UCL, London, United Kingdom; UniProt development, European Molecular Biology Laboratory European Bioinformatics Institute, Hinxton, United Kingdom; UniProt content, European Molecular Biology Laboratory European Bioinformatics Institute, Hinxton, United Kingdom; 4 Proteomics, European Molecular Biology Laboratory European Bioinformatics Institute, Hinxton, United Kingdom; Cardiovascular, King's College London, London,