title: Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family.
abstract: Familial LCAT deficiency (FLD) is a rare genetic disorder associated with corneal opacities, anaemia and proteinuria with renal failure. Here we report detailed analyses on plasma lipids, lipoproteins, and the molecular defect in two siblings from a Polish family presenting classical symptoms of FLD and their family members with newly discovered Val309Met mutation in exon 6 of LCAT gene. Both patients displayed low total (2.19 and 2.94 mmol/l) and HDL-cholesterol concentrations (0.52 and 0.48 mmol/l), low percentage of cholesteryl esters (CE) (11.1 and 12%), and decreased apo AI and apo AII serum levels. Low LDL-cholesterol, apo B and Lp(a) levels, and increased oleate/linoleate ratios in CE could be of importance in the development of atherosclerosis in these patients with low HDL-cholesterol. LCAT activity was 10% of normal, alpha-LCAT activity was 0, and LCAT concentration was undetectable by immunoassay. Plasma CETP activity was at lower limits of normal. PCR and sequence analysis of DNA from the proband and affected brother revealed a novel G-->A mutation in exon 6 of LCAT gene, which resulted in an amino acid substitution of valine for methionine (Val309Met). The proband and affected brother were both homozygous carriers, while the mother, siblings and children of patients were heterozygous carriers of a newly discovered mutation. This is the first LCAT mutation described in the Slavic population.
authors.affiliation: Department of Metabolic Diseases, Medical College, Jagiellonian University, 15 Kopernika Street, 31-501 Krakow, Poland. mmwalus@cyf-kr.edu.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Idzior-Waluś
authors.forename: Jacek
authors.initials: J
authors.lastname: Sieradzki
authors.forename: Gert
authors.initials: G
authors.lastname: Kostner
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Małecki
authors.forename: Tomasz
authors.initials: T
authors.lastname: Klupa
authors.forename: Teresa
authors.initials: T
authors.lastname: Wesołowska
authors.forename: Witold
authors.initials: W
authors.lastname: Rostworowski
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Hartwich
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Waluś
authors.forename: Aldona Dembińska
authors.initials: AD
authors.lastname: Kieć
authors.forename: Marek
authors.initials: M
authors.lastname: Naruszewicz
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001053:Apolipoproteins / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D002648:Child; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000097:blood / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009154:Mutation; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics*
chemical_list: D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008055:Lipids; D008074:Lipoproteins; D007862:Phosphatidylcholine-Sterol O-Acyltransferase