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 (Phe³⁸²→Val), a previously reported mutation (Thr³²¹→Met) and a common variant (Thr²⁰⁸→Ser) of the gene. Immunoreactive LCAT concentration (1.2 μg/ml), α-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.

Keywords:  HDL deficiency, Coronary artery disease, Familial defective apo B-100, Apolipoprotein E, Lp(a), Fish eye disease, Genetic mutation, LCAT

Abbreviations:  apo, apolipoprotein, CAD, coronary artery disease, CE, cholesteryl ester, CER, cholesterol esterification rate, FDB, familial defective apo B, FED, fish-eye disease, FH, familial hypercholesterolemia, FLD, familial LCAT deficiency, HDL, high-density lipoprotein, LCAT, lecithin:cholesterol acyltransferase, LDL, low-density lipoprotein, Lp (a), lipoprotein(a), MI, myocardial infarction, PCR, polymerase chain reaction, TG, triglyceride, UC, unesterified cholesterol