Cys209 ser mutation in the platelet membrane glycoprotein Ibα gene is associated with Bernard-Soulier syndrome

S. Simsek, P. Noris, M. Lozano, M. Pico, A. E G van dem Borne Kr., A. Ribera, D. Gallardo

Research output: Contribution to journalArticlepeer-review


Molecular genetic analysis has been performed on a patient with Bernard-Soulier syndrome (BSS). The patient had characteristically giant platelets and was deficient in the glycoprotein (GP) Ib/IX/V complex, the von Willebrand factor (vWf) receptor on platelets. Previous studies with monoclonal antibodies directed against GP Ibα (CD 42b) and GP IX (CD 42a) demonstrated the absence of GP Ibα and presence of small amounts of GP IX on the surface of the patient's platelets. In this study the presence of GP V (CD 42d) is also demonstrated. This indicates a defect in the α-subunit of glycoprotein Ib. Therefore polymerase chain reaction (PCR)-amplification of the genomic DNA coding for GP Ibα was performed. Nucleotide sequence analysis of the entire coding region of GP Ibα revealed a homozygous single base pair mutation T→ A, leading to a single amino acid substitution cysteine→ serine at position 209 of the mature protein. We took advantage of the Mse I target site in the mutant allele, created by the T → A mutation, to analyse all available family members. PCR-ASRA (allele-specific restriction enzyme analysis) using the restriction enzyme Mse L revealed the heterozygosity of the mother and the two children of the patient, whereas homozygosity of the patient for the Cys209Ser mutation was confirmed. The sister of the patient was not found to be a carrier of the mutant allele. The mutation identitied in the family studied, responsible for the deficiency of the GP Ib/lX/V complex, suggests that the cysteine at amino acid position 209 may be involved in disulphide bonding.

Original languageEnglish
Pages (from-to)839-844
Number of pages6
JournalBritish Journal of Haematology
Issue number4
Publication statusPublished - 1994


  • Bleeding disorder
  • BSS
  • Disulphide bonding
  • Giant platelets
  • Glycoprotein
  • Ibα
  • Molecular genetics
  • PCR
  • Point mutation

ASJC Scopus subject areas

  • Hematology


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