title: Bisalbuminaemia due to novel mutation at a critical residue involved in recycling; Albumin Lyon (510His→Arg).
abstract: OBJECTIVE
  To define the underlying cause of bisalbuminaemia in an individual presenting with spontaneous venous thrombosis.
  
  
  METHODS
  Plasma was examined by electrospray time-of-flight mass spectrometry (TOF MS) to assess albumin mutations and to quantify variant expression level. Tryptic peptide mapping and DNA sequencing were used to precisely define the mutation.
  
  
  RESULTS
  Whole protein MS indicated a 19Da increase in the mass of 50% of the albumin molecules suggesting a His→Arg substitution. A novel heterozygous 510His→Arg mutation was identified by peptide mass mapping and confirmed by DNA sequencing of exon 12 of the albumin gene.
  
  
  CONCLUSIONS
  The nature and location of the mutation suggest it would have no direct influence on haemostasis through altered warfarin binding or increased fibrinogen attachment and it appears to be incidental to the thrombotic phenotype. However the highly conserved His510 residue is recognised as being of critical importance in albumin recycling through interaction with its savaging neonatal Fc receptor. The normal albumin level of 41.1g/l and the coequal expression of albumin Lyon demonstrate that the conservative 510His→Arg substitution does not interfere with the pH dependant capture and release of albumin by the receptor.
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand; University of Otago, Christchurch School of Medicine, Christchurch, New Zealand. Electronic address: steve.brennan@otago.ac.nz.
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Brennan
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Howard C
authors.initials: HC
authors.lastname: Potter
authors.affiliation: Laboratoire d'hématologie, GHE, Hospices Civils de Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Hanss
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D001796:Blood Protein Disorders / Q000097:blood / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010449:Peptide Mapping / Q000379:methods*; D011961:Receptors, Fc / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods; D012709:Serum Albumin / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D012709:Serum Albumin; C100688:Fc receptor, neonatal
keywords: Albumin mutation; Albumin recycling; Neonatal Fc receptor; Protein mass spectrometry