A novel LCAT mutation (Phe382-->Val) in a kindred with familial LCAT deficiency and defective apolipoprotein B-100

M Nazeem Nanjee; Joseph Stocks; C Justin Cooke; Henri O F Molhuizen; Santica Marcovina; David Crook; John P Kastelein; Norman E Miller

doi:10.1016/s0021-9150(03)00241-7

A novel LCAT mutation (Phe382-->Val) in a kindred with familial LCAT deficiency and defective apolipoprotein B-100

Atherosclerosis. 2003 Sep;170(1):105-13. doi: 10.1016/s0021-9150(03)00241-7.

Authors

M Nazeem Nanjee¹, Joseph Stocks, C Justin Cooke, Henri O F Molhuizen, Santica Marcovina, David Crook, John P Kastelein, Norman E Miller

Affiliation

¹ 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

PMID: 12957688
DOI: 10.1016/s0021-9150(03)00241-7

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Alleles
Apolipoprotein A-I / blood
Apolipoprotein A-I / genetics
Apolipoprotein A-II / blood
Apolipoprotein A-II / genetics
Apolipoprotein B-100
Apolipoproteins B / genetics*
Apolipoproteins B / metabolism*
Apolipoproteins E / blood
Apolipoproteins E / genetics
Biomarkers / blood
Child
Cholesterol, HDL / blood
Cholesterol, HDL / genetics
Cholesterol, LDL / blood
Cholesterol, LDL / genetics
Coronary Disease / genetics
Coronary Disease / metabolism
Esterification
Female
Genetic Predisposition to Disease / genetics
Genotype
Humans
Lecithin Cholesterol Acyltransferase Deficiency / genetics*
Lecithin Cholesterol Acyltransferase Deficiency / metabolism*
Lipoprotein(a) / blood
Lipoprotein(a) / genetics
Lipoprotein-X / blood
Lipoprotein-X / genetics
Male
Middle Aged
Pedigree
Phosphatidylcholine-Sterol O-Acyltransferase / genetics*
Phosphatidylcholine-Sterol O-Acyltransferase / metabolism*
Point Mutation / genetics*
Polymorphism, Genetic / genetics
Sequence Analysis, DNA
Triglycerides / blood
Triglycerides / genetics

Substances

Apolipoprotein A-I
Apolipoprotein A-II
Apolipoprotein B-100
Apolipoproteins B
Apolipoproteins E
Biomarkers
Cholesterol, HDL
Cholesterol, LDL
Lipoprotein(a)
Lipoprotein-X
Triglycerides
Phosphatidylcholine-Sterol O-Acyltransferase