Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency

• Published in: Nature genetics Vol. 22; no. 4; pp. 336 - 345
• Main Authors: Molhuizen, Henri O.F, Brewer, Carl, van Dam, Marjel, Scherer, Stephen, Fichter, Keith, Frohlich, Jiri, Marcil, Michel, Morgan, Kenneth, Ashbourne-Excoffon, Katherine J.D, Clee, Susanne M, Kastelein, John J.P, Loubser, Odell, Mott, Stephanie, Zhang, Lin-Hua, Sensen, Christoph W, Denis, Maxime, Hayden, Michael R, Roomp, Kirsten, Yu, Lu, Collins, Jennifer A, Genest, Jacques, Pimstone, Simon, Koop, Ben, Martindale, Duane, Brooks-Wilson, Angela, Ouelette, B.F. Francis
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.08.1999
• Subjects: Adult; Amino Acid Sequence; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Base Sequence; Biological and medical sciences; Cholesterol, HDL - deficiency; Chromosomes, Human, Pair 9; Errors of metabolism; Female; Genetic Linkage; Genetic Markers; Glycoproteins - genetics; Glycoproteins - metabolism; Humans; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical sciences; Metabolic diseases; Models, Genetic; Molecular Sequence Data; Mutation; Pedigree; Physical Chromosome Mapping; Sequence Homology, Amino Acid; Tangier Disease - genetics; Genetic mapping; Human; Intracellular transport; Membrane protein; Deficiency; Metabolic diseases; Lipids; Cholesterol; Chromosome C9; Genetic disease; Gene; Hypocholesterolemia; Mutation; Lipoprotein HDL; ABC transporter
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/11905

Genes have a major role in the control of high-density lipoprotein (HDL) cholesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette transporter (ABC1). Familial HDL deficiency (FHA) is a more frequent cause of low HDL levels. On the basis of independent linkage and meiotic recombinants, we localized the FHA locus to the same genomic region as the TD locus. Mutations in ABC1 were detected in both TD and FHA, indicating that TD and FHA are allelic. This indicates that the protein encoded by ABC1 is a key gatekeeper influencing intracellular cholesterol transport, hence we have named it cholesterol efflux regulatory protein (CERP).