title: A case of Tangier disease with a novel mutation in the C-terminal region of ATP-binding cassette transporter A1.
abstract: Tangier disease (TD), a rare disorder characterized by extremely low levels of high density lipoprotein cholesterol (HDL-C), is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1) gene. Here, we describe a new patient with TD. The 42-year-old proband had obvious juvenile cataracts, mild hepatosplenomegaly, and an extremely low level of HDL-C (1 mg/dl), consistent with the diagnosis of TD. The proband was homozygous for a novel CTC6914-6TT --> 2203X mutation in the carboxy terminus of the ABCA1 protein. ApoAI-mediated cholesterol efflux from patient fibroblasts was markedly decreased compared to control, despite normal levels of protein expression. This indicates that this mutant protein is normally transcribed and exists as a stable product, yet is functionally defective. These results point to a critical role for the intracellular C-terminal region of the ABCA1 gene product in regulating cholesterol efflux and HDL-cholesterol levels.
authors.affiliation: Third Department of Internal Medicine, Hirosaki University School of Medicine, 5-Zaifu, Hirosaki 036-8562, Japan.
authors.forename: Jing-Zhi
authors.initials: JZ
authors.lastname: Guan
authors.forename: Naoki
authors.initials: N
authors.lastname: Tamasawa
authors.forename: Liam R
authors.initials: LR
authors.lastname: Brunham
authors.forename: Jun
authors.initials: J
authors.lastname: Matsui
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ochiai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Kenji
authors.initials: K
authors.lastname: Kudou
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D015153:Blotting, Western; D002386:Cataract / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D006529:Hepatomegaly / Q000235:genetics; D006801:Humans; D013163:Splenomegaly / Q000235:genetics; D013631:Tangier Disease / Q000235:genetics*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL