Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay

Ingrid Bartsch; Kirstin Sandrock; Francois Lanza; Paquita Nurden; Ina Hainmann; Anna Pavlova; Andreas Greinacher; Uta Tacke; Michael Barth; Anja Busse; Johannes Oldenburg; Martin Bommer; Brigitte Strahm; Andrea Superti-Furga; Barbara Zieger

doi:10.1160/TH11-05-0305

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(03): 475-483
DOI: 10.1160/TH11-05-0305

Platelets and Blood Cells

Schattauer GmbH

Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay

Ingrid Bartsch

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Kirstin Sandrock

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Francois Lanza

²Inserm UMR_S 949, Etablissement Français du Sang – Alsace (EFS-Alsace), Universitè de Strasbourg, Strasbourg, France

,

Paquita Nurden

³Centre de Rèfèrence des Pathologies Plaquettaires, Hôpital Cardiologique, Pessac, France

,

Ina Hainmann

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Anna Pavlova

⁴Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

,

Andreas Greinacher

⁵Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany

,

Uta Tacke

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Michael Barth

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Anja Busse

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Johannes Oldenburg

⁴Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

,

Martin Bommer

⁶Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany

,

Brigitte Strahm

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Andrea Superti-Furga

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Barbara Zieger

¹Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

› Author Affiliations

Abstract

Summary

The bleeding disorder Bernard-Soulier syndrome (BSS) is caused by mutations in the genes coding for the platelet glycoprotein GPIb/IX receptor. The septin SEPT5 is important for active membrane movement such as vesicle trafficking and exocytosis in non-dividing cells (i.e. platelets, neurons). We report on a four-year-old boy with a homozygous deletion comprising not only glycoprotein Ibβ (GP1BB) but also the SEPT5 gene, located 5’ to GP1BB. He presented with BSS, cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect. The homozygous deletion of GP1BB and SEPT5, which had been identified by PCR analyses, was confirmed by Southern analyses and denaturing HPLC (DHPLC). The parents were heterozygous for this deletion. Absence of GPIbβ and SEPT5 proteins in the patient’s platelets was illustrated using transmission electron microscopy. Besides decreased GPIb/IX expression, flow cytometry analyses revealedimpaired platelet granule secretion. Because the bleeding disorder was extremely severe, the boy received bone marrow transplantation (BMT) from a HLA-identical unrelated donor. After successful engraftment of BMT, he had no more bleedingepisodes. Interestingly, also his mental development improved strikingly after BMT. This report describes for the first time a patient with SEPT5 deficiency presenting with cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect.

keywords

Inherited / acquired platelet disorders - paediatric haemostasis - platelet glycoproteins - platelet pathology / inherited - aquired

Full Text

References

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