title: A novel ABCA1 nonsense mutation, R1270X, in Tangier disease associated with an unrecognised bleeding tendency.
abstract: The ATP binding cassette transporter A1 (ABCA1) is involved in the regulation of lipid trafficking and export of cholesterol from cells to high density lipoprotein (HDL). ABCA1 gene defects cause Tangier disease, an autosomal recessive disorder characterised by the absence of HDL-cholesterol in plasma, abnormal deposition of cholesteryl esters in the reticuloendothelial system, defective platelet dense and lysosomal granule release, and disordered cellular cholesterol efflux. We describe the case of a 62-year-old man with Tangier disease who presented with severe anaemia secondary to a spontaneous splenic haematoma. He underwent elective splenectomy without haemorrhage and his thrombocytopaenia resolved with a platelet count rising from 97 to 560 x 10(9)/L. Macroscopically, the resected spleen was enlarged with evidence of splenic haematoma. Histologic analysis of sections of spleen revealed lipid histiocytosis consistent with the diagnosis of Tangier disease. DNA sequence analysis revealed the subject to be a homozygote for a novel ABCA1 mutation c.4121C>T, which changes arginine 1270 to a stop codon (R1270X). In conclusion, we describe a case of Tangier disease in association with an unrecognised bleeding tendency, in a man homozygous for a novel ABCA1 gene mutation, R1270X.
authors.affiliation: Department of Core Clinical Pathology & Biochemistry, Royal Perth Hospital, Perth, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.forename: Ken
authors.initials: K
authors.lastname: Robertson
authors.forename: Lydia
authors.initials: L
authors.lastname: Ng
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Kattampallil
authors.forename: Donald
authors.initials: D
authors.lastname: Latchem
authors.forename: Peter C
authors.initials: PC
authors.lastname: Willsher
authors.forename: James
authors.initials: J
authors.lastname: Thom
authors.forename: Ross I
authors.initials: RI
authors.lastname: Baker
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D006470:Hemorrhage / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013631:Tangier Disease / Q000150:complications* / Q000235:genetics*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018389:Codon, Nonsense