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


METHODS
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).


RESULTS
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.


CONCLUSIONS
T13M mutation of LCAT gene causes FED.
Miida
Takashi
T
Division of Clinical Preventive Medicine, Department of Community Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata, Niigata 951-8510, Japan. miida@med.niigata-u.ac.jp
Zhang
Bo
B
Obayashi
Konen
K
Seino
Utako
U
Zhu
Ying
Y
Ito
Takako
T
Nakamura
Yuichi
Y
Okada
Masahiko
M
Saku
Keijiro
K
D000328:Adult; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005128:Eye Diseases / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D013912:Threonine / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D008074:Lipoproteins; D008075:Lipoproteins, HDL; D013912:Threonine; D007862:Phosphatidylcholine-Sterol O-Acyltransferase