Clinical variant of Tangier disease in Japan: mutation of the ABCA1 gene in hypoalphalipoproteinemia with corneal lipidosis.
Despite progress in molecular characterization, specific diagnoses of disorders belonging to a group of inherited hypoalphalipoproteinemias, i.e., apolipoprotein AI deficiency, lecithin-cholesterol acyltransferase deficiency, Tangier disease (TD), and familial high-density lipoprotein (HDL) deficiency, remain difficult on a purely clinical basis. Several TD patients were recently found to be homozygous for mutations in the ABCA1 gene. We have documented here a clinical variant of TD in a Japanese patient who manifested corneal lipidosis and premature coronary artery disease as well as an almost complete absence of HDL-cholesterol, by identifying a novel homozygous ABCA1 mutation (R1680W). We propose that patients with apparently isolated HDL deficiency who are found to carry ABCA1 mutations may in fact belong to a category of TD patients whose phenotypic features are only partially expressed, and that a number of hidden clinical variants of TD might exist among other HDL deficiency patients who have escaped correct clinical diagnosis.
Division of Internal Medicine, Hokkaido Hospital for Social Health Insurance, Sapporo, Japan.
Jun
J
Ishii
Makoto
M
Nagano
Takeshi
T
Kujiraoka
Mitsuaki
M
Ishihara
Tohru
T
Egashira
Daisuke
D
Takada
Masahiro
M
Tsuji
Hiroaki
H
Hattori
Mitsuru
M
Emi
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D003316:Corneal Diseases / Q000503:physiopathology*; D006801:Humans; D007564:Japan; D008064:Lipidoses / Q000235:genetics* / Q000503:physiopathology; D008075:Lipoproteins, HDL / Q000172:deficiency; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D013631:Tangier Disease / Q000235:genetics* / Q000503:physiopathology
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008075:Lipoproteins, HDL