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.
Ishii
Jun
J
Division of Internal Medicine, Hokkaido Hospital for Social Health Insurance, Sapporo, Japan.
Nagano
Makoto
M
Kujiraoka
Takeshi
T
Ishihara
Mitsuaki
M
Egashira
Tohru
T
Takada
Daisuke
D
Tsuji
Masahiro
M
Hattori
Hiroaki
H
Emi
Mitsuru
M
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