Semin Thromb Hemost 2000; Volume 26(Number 01): 053-060
DOI: 10.1055/s-2000-9804
Copyright © 2000 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4663)

Molecular Pathogenesis of Bernard-Soulier Syndrome

Tomohiro Hayashi, Keijiroh Suzuki
  • Third Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan
Further Information

Publication History

Publication Date:
31 December 2000 (online)

 

ABSTRACT

Bernard-Soulier syndrome (BSS), a hereditary qualitative platelet disorder, is now proved to be caused by a qualitative or quantitative abnormality of the platelet glycoprotein (GP) Ib/IX/V complex. We investigated the genetic background of two Japanese females with BSS and identified the molecular defects underlying this disease. The first case was a single base pair deletion within seven adenine repeats at position 4464-4470 (EMBL, no. M22403) of the GPIbα gene resulting in a frameshift and a premature stop codon. The second case was a single T→C substitution at nucleotide 1856 (EMBL, no. M80478) of the GPIX gene resulting in Phe55 (TTT)→Ser(TCT) substitution. The latter case is of interest in considering the pathogenesis of BSS, because all four GPs consisting of the GPIb/IX/V complex have the same structural unit called leucine-rich repeat (LRR). Because this mutation is located within the LRR of the GPIX polypeptide, Phe55→Ser substitution may result in an alteration of the LRR that leads to impaired surface expression of the GPIb/IX/V complex. To clarify the effect of this mutation on surface expression of the GPIb/IX complex, we performed transfection studies with a plasmid having this mutation. Mutant GPIX could not increase surface expression of the GPIb/IX complex, thus demonstrating an important role of the LRR of the GPIX polypeptide during biosynthesis.

KEYWORD

Bernard-Soulier syndrome - platelet glycoprotein - GPIb/IX/V complex - leucine-rich repeat - missense mutation

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