Background: Lecithin-cholesterol acyltransferase (LCAT) esterifies free cholesterol (FC) in plasma and plays a crucial role in the maturation of preβ1-HDL (lipid-poor HDL) into α-migrating HDL (spherical HDL). Natural mutations of LCAT gene cause familial LCAT deficiency (FLD) or fish-eye disease (FED). The relationship between mutations and their phenotypes gives important clues to the functions of specific regions of LCAT. We investigated the first homozygous case with a substitution of threonine to methionine at codon 13 (T13M) of LCAT gene. Methods: We evaluated LCAT activity, LCAT distribution among HDL subfractions and conversion of preβ1-HDL to α-migrating HDL by native two-dimensional gel electrophoresis (N-2DGE). Results: The proband had corneal opacity, severe hypo-α-lipoproteinemia, half-normal LCAT activity and near normal cholesteryl ester/total cholesterol (TC) ratio in plasma. These features were characteristic of FED. Plasma preβ1-HDL concentration was near normal, but not converted to α-migrating HDL during 37 o C incubation. As expected, α-migrating HDL (especially large particles) was markedly reduced. In the immunoblot against LCAT, the small α-migrating HDL from the proband had much less LCAT in this patient than in controls. Conclusion: T13M mutation of LCAT gene causes FED.