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Bernard–Soulier syndrome caused by a novel GP1BB variant and 22q11.2 deletion

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Abstract

Bernard–Soulier syndrome (BSS) is caused by defects in GP1BA, GP1BB, or GP9 genes. Patients with 22q11.2 deletion syndrome (22q11.2DS) are obligate carriers of BSS because GP1BB resides on chromosome 22q11.2. A 15-month-old girl without bleeding symptoms had giant platelets and thrombocytopenia. Physical findings and macrothrombocytopenia suggested 22q11.2DS, which was confirmed by fluorescence in situ hybridization. Flow cytometry showed decreased GPIbα on the platelets. Gene panel testing revealed a novel variant in GP1BB, p.(Val169_Leu172del). These findings confirmed that the patient had BSS. This case suggests that any patient with 22q11.2DS and macrothrombocytopenia should be further tested for BSS.

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Data availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

References

  1. Andrews RK, Berndt MC. Bernard-Soulier syndrome: an update. Semin Thromb Hemost. 2013;39:656–62.

    Article  CAS  PubMed  Google Scholar 

  2. Kunishima S, Kamiya T, Saito H. Genetic abnormalities of Bernard-Soulier syndrome. Int J Hematol. 2002;76:319–27.

    Article  CAS  PubMed  Google Scholar 

  3. Andrews RK, Gardiner EE, Shen Y, Whisstock JC, Berndt MC. Glycoprotein Ib-IX-V. Int J Biochem Cell Biol. 2003;35:1170–4.

    Article  CAS  PubMed  Google Scholar 

  4. Pham A, Wang J. Bernard-Soulier syndrome: an inherited platelet disorder. Arch Pathol Lab Med. 2007;131:1834–6.

    Article  PubMed  Google Scholar 

  5. McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore) 2011;90:1–18.

  6. Budarf ML, Konkle BA, Ludlow LB, Michaud D, Li M, Yamashiro DJ, et al. Identification of a patient with Bernard– Soulier syndrome and a deletion in the DiGeorge/velo-cardio-facial chromosomal region in 22q11.2. Hum Mol Genet. 1995;4:763–766.

  7. Kanamaru Y, Uchiyama T, Kaname T, Yanagi K, Ohara O, Kunishima S, et al. ETV6-related thrombocytopenia associated with a transient decrease in von Willebrand factor. Int J Hematol. 2021;114:297–300.

    Article  CAS  PubMed  Google Scholar 

  8. Savoia A, Kunishima S, De Rocco D, Zieger B, Rand ML, Pujol-Moix N, et al. Spectrum of the mutations in Bernard-Soulier syndrome. Hum Mutat. 2014;35:1033–45.

    Article  CAS  PubMed  Google Scholar 

  9. Kenny D, Morateck PA, Gill JC, Montgomery RR. The critical interaction of glycoprotein (GP) IBbeta with GPIX-a genetic cause of Bernard-Soulier syndrome. Blood. 1999;93:2968–75.

    Article  CAS  PubMed  Google Scholar 

  10. Hillmann A, Nurden A, Nurden P, Combrié R, Claeyssens S, Moran N, et al. A novel hemizygous Bernard-Soulier Syndrome (BSS) mutation in the amino terminal domain of glycoprotein (GP)Ibbeta–platelet characterization and transfection studies. Thromb Haemost. 2002;88:1026–32.

    Article  CAS  PubMed  Google Scholar 

  11. Nurden AT, Combrié R, Claeyssens S, Nurden P. Heterozygotes in the Bernard– Soulier syndrome do not necessarily have giant platelets or thrombocytopenia. Br J Haematol. 2003;120:716–7.

    Article  CAS  PubMed  Google Scholar 

  12. Tang J, Stern-Nezer S, Liu PC, Matyakhina L, Riordan M, Luban NL, et al. Mutation in the leucine-rich repeat C-flanking region of platelet glycoprotein Ib beta impairs assembly of von Willebrand factor receptor. Thromb Haemost. 2004;92:75–88.

    Article  CAS  PubMed  Google Scholar 

  13. Bartsch I, Sandrock K, Lanza F, Nurden P, Hainmann I, Pavlova A, et al. Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay. Thromb Haemost. 2011;106:475–83.

    Article  CAS  PubMed  Google Scholar 

  14. Kunishima S, Imai T, Kobayashi R, Kato M, Ogawa S, Saito H. Bernard-Soulier syndrome caused by a hemizygous GPIbβ mutation and 22q11.2 deletion. Pediatr Int. 2013;55: 434–7.

  15. Souto Filho JTD, Ribeiro HAA, Fassbender IPB, Ribeiro JMMC, Ferreira Júnior WDS, Figueiredo LCS. Bernard-Soulier syndrome associated with 22q11.2 deletion and clinical features of DiGeorge/velocardiofacial syndrome. Blood Coagul Fibrinolysis. 2019;30: 423–425.

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Acknowledgements

The authors express their gratitude to the participating patient and her parents. They are grateful to the senior medical editor at the Center for Postgraduate Education and Training at the National Center for Child Health and Development for English language review.

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Authors and Affiliations

  1. Center for Postgraduate Education and Training, National Center for Child Health and Development (NCCHD), Tokyo, Japan

    Rintaro Nagoshi & Akira Ishiguro

  2. Division of Hematology, Center for Postgraduate Education and Training, NCCHD, 2-10-1 Okura, Setagaya-Ku, Tokyo, 157-8535, Japan

    Atsushi Sakamoto & Akira Ishiguro

  3. Department of Pediatric Hematology and Oncology, National Hospital Organization Shikoku Medical Center for Children and Adults, Kagawa, Japan

    Tsuyoshi Imai

  4. Department of Human Genetics, NCCHD, Tokyo, Japan

    Toru Uchiyama

  5. Department of Genome Medicine, NCCHD, Tokyo, Japan

    Tadashi Kaname

  6. Department of Medical Technology, School of Health Sciences, Gifu University of Medical Science, Gifu, Japan

    Shinji Kunishima

Authors
  1. Rintaro Nagoshi
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  2. Atsushi Sakamoto
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  3. Tsuyoshi Imai
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  4. Toru Uchiyama
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  5. Tadashi Kaname
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  6. Shinji Kunishima
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  7. Akira Ishiguro
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Correspondence to Atsushi Sakamoto.

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New findings: We described a patient with compound heterozygous Bernard-Soulier syndrome (BSS) caused by a novel GPIBB variant and 22q11.2 deletion syndrome (22q11.2DS). To our knowledge, previously reported cases of BSS associated with 22q11.2DS have bleeding symptoms. However, this case had no bleeding symptoms, despite decreased expression of GPIbβ. We suggest that any patient with 22q11.2DS associated with macrothrombocytopenia should be investigated for the presence of BSS using FCM and DNA sequencing, regardless of the presence or absence of bleeding symptoms.

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Nagoshi, R., Sakamoto, A., Imai, T. et al. Bernard–Soulier syndrome caused by a novel GP1BB variant and 22q11.2 deletion. Int J Hematol (2024). https://doi.org/10.1007/s12185-024-03768-2

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  • DOI: https://doi.org/10.1007/s12185-024-03768-2

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