Bernard-Soulier syndrome with a homozygous 13 base pair deletion in the signal peptide-coding region of the platelet glycoprotein Ibβ gene

Reiko Watanabe, Toshiyuki Ishibashi, Yurie Saitoh, Tsutomu Shichishima, Yukio Maruyama, Yasuhiro Enomoto, Makoto Handa, Atsushi Oda, Hironobu Ambo, Mitsuru Murata, Yasuo Ikeda

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We report a family with Bernard-Soulier syndrome with a homozygous mutation within the GPIbβ gene. The proband was a 24-year-old Japanese male who has suffered from life-long bleeding tendency. The patient's sister also had severe bleeding episodes. The proband and the affected sister had no apparent complications including organic or skeletal anomaly, or mental disturbance. They had thrombocytopenia [(35-40) × 109/l] with giant platelets. In addition to platelet size, electron microscopic analysis revealed abnormalities in the internal structures of platelets. Ristocetin-induced platelet aggregation was defective. Flow cytometric analysis and western blot analysis showed that glycoprotein IX was nearly absent in platelets, whereas GPIbα and GPV were detectable. Genetic studies revealed a 13 base pair deletion in the signal peptide-coding sequence of GPIbβ. The deletion would cause a frame-shift, resulting in the appearance of a stop codon following an indifferent polypeptide sequence. Analysis of platelet RNA showed that the mutant GPIbβ gene was transcribed. The propositus and his affected sister were homozygous for the deletion, whereas their unaffected father and mother were heterozygotes. The molecular defects of this family would help understand the relevance of GPIbβ for complex formation of the glycoprotein Ib/IX/V receptor.

Original languageEnglish
Pages (from-to)387-394
Number of pages8
JournalBlood Coagulation and Fibrinolysis
Volume14
Issue number4
DOIs
Publication statusPublished - 2003 Jun

Fingerprint

Bernard-Soulier Syndrome
Platelet Glycoprotein GPIb-IX Complex
Platelet Membrane Glycoproteins
Protein Sorting Signals
Base Pairing
Blood Platelets
Siblings
Genes
Ristocetin
Hemorrhage
Terminator Codon
Heterozygote
Platelet Aggregation
Fathers
Thrombocytopenia
Glycoproteins
Western Blotting
Mothers
RNA
Electrons

Keywords

  • Bernard-Soulier syndrome
  • Genetics
  • GPIbβ
  • Mutation
  • Platelet

ASJC Scopus subject areas

  • Hematology

Cite this

Bernard-Soulier syndrome with a homozygous 13 base pair deletion in the signal peptide-coding region of the platelet glycoprotein Ibβ gene. / Watanabe, Reiko; Ishibashi, Toshiyuki; Saitoh, Yurie; Shichishima, Tsutomu; Maruyama, Yukio; Enomoto, Yasuhiro; Handa, Makoto; Oda, Atsushi; Ambo, Hironobu; Murata, Mitsuru; Ikeda, Yasuo.

In: Blood Coagulation and Fibrinolysis, Vol. 14, No. 4, 06.2003, p. 387-394.

Research output: Contribution to journalArticle

Watanabe, R, Ishibashi, T, Saitoh, Y, Shichishima, T, Maruyama, Y, Enomoto, Y, Handa, M, Oda, A, Ambo, H, Murata, M & Ikeda, Y 2003, 'Bernard-Soulier syndrome with a homozygous 13 base pair deletion in the signal peptide-coding region of the platelet glycoprotein Ibβ gene', Blood Coagulation and Fibrinolysis, vol. 14, no. 4, pp. 387-394. https://doi.org/10.1097/00001721-200306000-00010
Watanabe, Reiko ; Ishibashi, Toshiyuki ; Saitoh, Yurie ; Shichishima, Tsutomu ; Maruyama, Yukio ; Enomoto, Yasuhiro ; Handa, Makoto ; Oda, Atsushi ; Ambo, Hironobu ; Murata, Mitsuru ; Ikeda, Yasuo. / Bernard-Soulier syndrome with a homozygous 13 base pair deletion in the signal peptide-coding region of the platelet glycoprotein Ibβ gene. In: Blood Coagulation and Fibrinolysis. 2003 ; Vol. 14, No. 4. pp. 387-394.
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