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

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.