MOLECULAR DIAGNOSIS OF LECITHIN - CHOLESTEROL ACYLTRANSFERASE DEFICIENCY IN A PRESYMPTOMATIC PROBAND

We report the molecular diagnosis of a lecithin : cholesterol acyltran sferase deficiency in a 12-year old proband with a high-density lipopr otein deficiency. The increased percentage of free cholesterol in plas ma and high-density lipoprotein indicated an inherited lecithin : chol esterol acyltransferase deficiency as the underlying cause. This diagn osis was confirmed by a low plasma lecithin : cholesterol acyltransfer ase activity and a combination of genetic analyses which demonstrated compound heterozygosity for two mutations in the lecithin : cholestero l acyltransferase gene of the proband. One was a previously unreported 2 bp deletion leading to a stop signal in codon 77 and the other a po int mutation causing Arg 135 --> Gin transition. To our knowledge, thi s is the first diagnosis of lecithin : cholesterol acyltransferase def iciency in a pre-symptomatic patient. Whether the proband will develop signs of complete lecithin : cholesterol acyltransferase deficiency o r the milder form (Fish Eye Disease) is uncertain, although the former possibility is more likely. The risk of premature atherosclerosis con ferred by lecithin : cholesterol acyltransferase deficiency is not wel l established. The proband will need to be carefully monitored in the future.