title: A Novel Homozygous c.800C>G Substitution in GP1BA Exon 2 in a Kuwaiti Family with Bernard-Soulier Syndrome.
abstract: BACKGROUND
  Bernard-Soulier syndrome (BSS) is a congenital bleeding disorder characterised by thrombocytopenia, giant platelets and decreased platelet adhesion resulting from genetic alterations of the glycoprotein (GP) Ib/IX/V complex.
  
  
  OBJECTIVE
  Three sisters with a lifelong bleeding history and a provisional diagnosis of BSS were referred for further characterisation of their bleeding diathesis. The siblings' symptoms varied in severity from skin and gum bleeding to menorrhagia associated with iron-deficiency anaemia requiring regular transfusion of red cells and platelets. The parents were consanguineous but did not demonstrate any bleeding disorder.
  
  
  METHODS
  The family were investigated using standard haematological techniques, platelet aggregometry, platelet membrane GP analysis and DNA sequencing of the genes encoding the GPIb/IX complex.
  
  
  RESULTS
  All 3 sisters had thrombocytopenia and giant platelets. Platelet aggregation and flow cytometry studies confirmed the lack of aggregation with ristocetin and a markedly reduced GPIb/IX surface expression. Molecular analysis demonstrated a novel homozygous c.800C>G substitution in GP1BA exon 2 leading to a serine 267 Ter stop codon in all 3 siblings.
  
  
  CONCLUSIONS
  A novel, nonsense mutation was identified as the cause of the bleeding disorder in this family. This is the first reported BSS mutation identified in a family from Kuwait.
authors.affiliation: Haemostasis and Thrombosis Unit, Imperial College Healthcare, St. Thomas' Hospital, London, UK.
authors.forename: Abdul
authors.initials: A
authors.lastname: Shlebak
authors.forename: Anthony
authors.initials: A
authors.lastname: Poles
authors.forename: Richard
authors.initials: R
authors.lastname: Manning
authors.forename: Shaikha
authors.initials: S
authors.lastname: Almuhareb
authors.forename: Josu
authors.initials: J
authors.lastname: De La Funte
authors.forename: Mike
authors.initials: M
authors.lastname: Mitchell
authors.forename: Geoff
authors.initials: G
authors.lastname: Lucas
mesh_terms: D000293:Adolescent; D000328:Adult; D001606:Bernard-Soulier Syndrome / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D005091:Exons; D005260:Female; D005434:Flow Cytometry; D006720:Homozygote; D006801:Humans; D007730:Kuwait; D008297:Male; D008875:Middle Aged; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor