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International Journal of Hematology

, Volume 80, Issue 1, pp 83–90 | Cite as

Glanzmann Thrombasthenia Associated with a 21-Amino Acid Deletion (Leu817-Gln837) in Glycoprotein IIb due to Abnormal Splicing in Exon 25

  • Tetsuro-Takahiro Fujimoto
  • Mihoko Sora
  • Kazuko Ide
  • Miyoko Mizushima
  • Masashi Mita
  • Shinichiro Nishimura
  • Kazuhiro Ueda
  • Kingo Fujimura
Article

Abstract

We report a novel genetic defect in a Japanese patient with type I Glanzmann thrombasthenia.The glycoprotein (GP) IIb complementary DNA (cDNA) from platelet messenger RNA had a 63-base pair deletion in the 5′ boundary of exon 25, resulting in an in-frame deletion of 21 amino acid residues (Leu817-Gln837) in the calf-2 domain.The deleted region was present in the genomic DNA, but the splice acceptor site (AG) of exon 25 was mutated to AC, leading to the use of an AG sequence in the middle of exon 25 as an abnormal cryptic splice acceptor site. The effect of this deletion on protein synthesis was further analyzed. Mutant GPIIb-IIIa complexes were not detected on the surfaces of cells cotransfected with cDNAs of mutant GPIIb and normal GPIIIa. Mutant pro-GPIIb was detected in cell lysates and was coimmunoprecipitated with an anti-GPIIb-IIIa complex antibody. Immunostaining demonstrated that the mutant pro-GPIIb colocalized with an endoplasmic reticulum protein, calnexin, within the cells. These results indicate that complex formation was not completely prevented and that impairment of the subsequent transport was the major reason for the defect in cell surface expression. The data suggest that the GPIIb calf-2 domain is important for intracellular transport of GPIIb-IIIa complexes.

Key words

Glanzmann thrombasthenia Platelets GPIIb-IIIa complex Intracellular transport Calf-2 domain 

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Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Tetsuro-Takahiro Fujimoto
    • 1
  • Mihoko Sora
    • 1
  • Kazuko Ide
    • 1
  • Miyoko Mizushima
    • 1
  • Masashi Mita
    • 1
  • Shinichiro Nishimura
    • 2
  • Kazuhiro Ueda
    • 2
  • Kingo Fujimura
    • 1
  1. 1.Department of Hematology and Oncology, Division of Clinical PharmacotherapeuticsProgram for Applied BiomedicineJapan
  2. 2.Department of Pediatrics, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan

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