Point mutation in a Leucine-rich repeat of platelet glycoprotein Ibα resulting in the Bernard-Soulier syndrome

Jerry Ware, Susan R. Russell, Patrizia Marchese, Mitsuru Murata, Mario Mazzucato, Luigi De Marco, Zaverio M. Ruggeri

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114 Citations (Scopus)


Leucine-rich repeats are a conserved structural motif, of yet undefined significance, found in a group of proteins from different species. Among these are the four components of the human platelet glycoprotein Ib-IX-V complex, a membrane receptor that performs an essential role in the thrombogenic function of platelets by interacting with the adhesive protein, von Willebrand factor. We have found that a single amino acid substitution (Ala156 → Val) within one of the six leucine-rich repeats in the α-subunit of glycoprotein Ib results in a variant form of the congenital bleeding disorder, Bernard-Soulier syndrome, characterized by giant dysfunctional platelets. Genetic studies of the propositus and his family members were complemented by immunological and functional analysis of expressed recombinant GP Ibα fragments to demonstrate that the observed mutation is the cause of defective von Willebrand factor binding. These studies define the molecular basis of the Bernard-Soulier syndrome within this family and demonstrate that structural integrity of a leucine-rich repeat is necessary for normal function of the glycoprotein Ib-IX-V receptor complex and, possibly, for normal platelet morphology.

Original languageEnglish
Pages (from-to)1213-1220
Number of pages8
JournalJournal of Clinical Investigation
Issue number3
Publication statusPublished - 1993 Sept
Externally publishedYes


  • Bleeding disorder
  • Giant platelets
  • Platelet adhesion
  • Thrombosis
  • Von Willebrand factor

ASJC Scopus subject areas

  • Medicine(all)


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