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T13M mutation of lecithin-cholesterol acyltransferase gene causes fish-eye disease.

Research paper by Takashi T Miida, Bo B Zhang, Konen K Obayashi, Utako U Seino, Ying Y Zhu, Takako T Ito, Yuichi Y Nakamura, Masahiko M Okada, Keijiro K Saku

Indexed on: 30 Apr '04Published on: 30 Apr '04Published in: Clinica Chimica Acta



Abstract

Lecithin-cholesterol acyltransferase (LCAT) esterifies free cholesterol (FC) in plasma and plays a crucial role in the maturation of prebeta1-HDL (lipid-poor HDL) into alpha-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.We evaluated LCAT activity, LCAT distribution among HDL subfractions and conversion of prebeta1-HDL to alpha-migrating HDL by native two-dimensional gel electrophoresis (N-2DGE).The proband had corneal opacity, severe hypo-alpha-lipoproteinemia, half-normal LCAT activity and near normal cholesteryl ester/total cholesterol (TC) ratio in plasma. These features were characteristic of FED. Plasma prebeta1-HDL concentration was near normal, but not converted to alpha-migrating HDL during 37 degrees C incubation. As expected, alpha-migrating HDL (especially large particles) was markedly reduced. In the immunoblot against LCAT, the small alpha-migrating HDL from the proband had much less LCAT in this patient than in controls.T13M mutation of LCAT gene causes FED.

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