A novel missense mutation in ABCA1 results in altered protein trafficking and reduced phosphatidylserine translocation in a patient with Scott syndrome

Blood. 2005 Jul 15;106(2):542-9. doi: 10.1182/blood-2004-05-2056. Epub 2005 Mar 24.


Scott syndrome (SS) is a bleeding disorder characterized by a failure to expose phosphatidylserine (PS) to the outer leaflet of the platelet plasma membrane. Because the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) is implicated in the exofacial translocation of PS, we assessed its role in the pathophysiology of a patient with SS. Substantially reduced levels of ABCA1 mRNA were found in the patient's leukocytes, compared with controls. The SS patient was heterozygous for a novel missense mutation c.6064G>A (ABCA1 R1925Q), absent from unaffected family members and controls. Both mutant and wild-type alleles were reduced in mRNA expression, and no causative mutation for this phenomenon was identified in the ABCA1 gene or its proximal promoter, suggesting a putative second mutation in a trans-acting regulatory gene may also be involved in the disorder in this patient. In vitro expression studies showed impaired trafficking of ABCA1 R1925Q to the plasma membrane. Overexpression of wild-type ABCA1 in SS lymphocytes complemented the Ca2+-dependent PS exposure at the cell surface. These data identify a mutation in ABCA1 that contributes to the defective PS translocation phenotype in our patient with SS.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / blood*
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Base Sequence
  • Biological Transport, Active / drug effects
  • Blood Coagulation Disorders, Inherited / blood*
  • Blood Coagulation Disorders, Inherited / genetics*
  • Blood Coagulation Disorders, Inherited / metabolism
  • Calcium / pharmacology
  • Cell Line
  • DNA / genetics
  • Female
  • Gene Expression
  • Genetic Complementation Test
  • Humans
  • In Vitro Techniques
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense*
  • Pedigree
  • Phosphatidylserines / blood
  • Phosphatidylserines / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid


  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Phosphatidylserines
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • DNA
  • Calcium