title: Molecular basis of Bernard-Soulier syndrome in 27 patients from India.
abstract: BACKGROUND
  Bernard-Soulier syndrome (BSS) is an extremely rare (1:1 million) bleeding disorder of platelet adhesion, caused by defects in the glycoprotein (GP)Ib/IX/V complex.
  
  
  METHODS
  The diagnosis in 27 patients was based on low platelet count, presence of giant platelets and aggregometry studies. Flow cytometry to assess the surface GPIb/IX/V complex showed reduced (7.7-57%) expression. gDNA was screened for mutations in the GPIBA, GPIBB, GP9 genes using PCR-conformation sensitive gel electrophoresis (CSGE).
  
  
  RESULTS
  Thirteen different disease-causing mutations, including missense (54%), frameshifts (38%) and nonsense (8%) mutations, were identified in 27 patients. Eleven of them were novel including five novel frameshifts (GPIbα: p.Gln97_98fsX113, p.Pro402_403fsX52; GPIbβ: p.Arg17fsX14; GPIX: p.Gly24fsX43, p. Pro130fs, a nonsense mutation (GPIX, p.94, Gln>X) and five novel missense mutations (GPIbα: p.492, Tyr>His; GPIbβ: p.65, Pro>Arg, p.129, Gln>His, p.132, Leu>Pro; GPIX: p.55, Phe>Cys). Interestingly, four common mutations, Cys8Arg (n = 6) and Phe55Ser (n = 2), Phe55Cys (n = 2) in GPIX and a novel 22-bp deletion in the GPIBB gene predicting p.Arg17fsX 14 (n = 10) were seen in 20 patients.
  
  
  CONCLUSIONS
  The molecular data presented here is the largest series of BSS patients to be reported so far, adding significantly to the mutation database of this condition and also useful for its genetic diagnosis in India.
authors.affiliation: Department of Hematology, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: E
authors.initials: E
authors.lastname: Sumitha
authors.forename: G R
authors.initials: GR
authors.lastname: Jayandharan
authors.forename: S
authors.initials: S
authors.lastname: David
authors.forename: R R
authors.initials: RR
authors.lastname: Jacob
authors.forename: G
authors.initials: G
authors.lastname: Sankari Devi
authors.forename: B
authors.initials: B
authors.lastname: Bargavi
authors.forename: S
authors.initials: S
authors.lastname: Shenbagapriya
authors.forename: S C
authors.initials: SC
authors.lastname: Nair
authors.forename: A
authors.initials: A
authors.lastname: Abraham
authors.forename: B
authors.initials: B
authors.lastname: George
authors.forename: A
authors.initials: A
authors.lastname: Viswabandya
authors.forename: V
authors.initials: V
authors.lastname: Mathews
authors.forename: M
authors.initials: M
authors.lastname: Chandy
authors.forename: A
authors.initials: A
authors.lastname: Srivastava
mesh_terms: D000293:Adolescent; D000328:Adult; D001606:Bernard-Soulier Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D005434:Flow Cytometry; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D010974:Platelet Aggregation; D010976:Platelet Count; D010979:Platelet Function Tests; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor