title: A novel LCAT mutation (Phe382-->Val) in a kindred with familial LCAT deficiency and defective apolipoprotein B-100.
abstract: We studied a four-generation family (17 subjects) with familial lecithin:cholesterol acyltransferase (LCAT) deficiency. A 30-year-old Caucasian male with corneal clouding and HDL cholesterol <0.1 mmol/l was a compound heterozygote for a novel mutation (Phe(382)-->Val), a previously reported mutation (Thr321-->Met) and a common variant (Thr208-->Ser) of the gene. Immunoreactive LCAT concentration (1.2 microg/ml), alpha-LCAT activity (13 nmol/ml per h) and cholesterol esterification rate (CER) (14 nmol/ml per h) in his plasma were, respectively, 14, 8 and 14% of the mean values in healthy subjects. The proband and 13 of his relatives also had familial defective apo B (FDB, Arg3500-->Gln). Six subjects had LCAT Phe382-->Val in combination with FDB. Plasma lipoprotein(a) (Lp(a)) was 24 nmol/l in the proband and 46-211 nmol/l in his father and siblings, consistent with expression of the 16 kringle 4 isoform. The proband had no signs of coronary heart disease (CHD), but his father, a paternal uncle and a female cousin had CHD before age 38 years.
authors.affiliation: Cardiovascular Biochemistry Unit, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK. nazeem.nanjee@med.va.gov
authors.forename: M Nazeem
authors.initials: MN
authors.lastname: Nanjee
authors.forename: Joseph
authors.initials: J
authors.lastname: Stocks
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Cooke
authors.forename: Henri O F
authors.initials: HO
authors.lastname: Molhuizen
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.forename: David
authors.initials: D
authors.lastname: Crook
authors.forename: John P
authors.initials: JP
authors.lastname: Kastelein
authors.forename: Norman E
authors.initials: NE
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics / Q000378:metabolism; D004951:Esterification; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000235:genetics* / Q000378:metabolism*; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics; D008073:Lipoprotein-X / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D008073:Lipoprotein-X; D014280:Triglycerides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase