title: Novel ABCA1 compound variant associated with HDL cholesterol deficiency.
abstract: The recent discovery of an ATP-binding cassette transporter, ABCA1, as an important regulator of high density lipoprotein (HDL) metabolism and reverse cholesterol transport has facilitated the identification of novel variants associated with HDL cholesterol deficiency states. We identified a subject with HDL cholesterol deficiency (4 mg/dl) who developed and died of complications related to cerebral amyloid angiopathy (CAA). The proband had a compound heterozygous mutation. One mutation was a G3295T substitution with conversion of asparagine to tyrosine (D1099Y) in ABCA1. The single-base substitution at codon 1099 resulted in the abolition of an RsaI cleavage site. The proband and affected individuals having another mutation were heterozygotes for T5966C with phenylalanine converted to serine (F2009S). The presence of the T5966C mutation was detected by restriction digestion with HinfI. These variants were not identified in over 400 chromosomes of healthy subjects. In the kindred, family members heterozygous for the ABCA1 variant exhibited low levels of HDL cholesterol. Direct sequencing of all coding regions and splice site junctions of other HDL candidate genes revealed no additional mutations, indicating that combined defective ABCA1 alleles may result in familial HDL deficiency.
authors: Department of Medicine, University of Maryland and Veterans Administration Medical Center, 22 S. Greene St., S3B06 Baltimore 21201, USA.
authors: Seung
authors: S
authors: Ho Hong
authors: Jeffrey
authors: J
authors: Rhyne
authors: Karen
authors: K
authors: Zeller
authors: Michael
authors: M
authors: Miller
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D016657:Cerebral Amyloid Angiopathy / Q000097:blood / Q000150:complications / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000172:deficiency*; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015183:Restriction Mapping
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL