New gene mutation identified in Bernard-Soulier syndrome patient

By Dr Jodie Abramovitch

Bernard-Soulier syndrome (BSS) is a rare condition in which blood does not clot properly leading to increased bleeding. The underlying cause of this condition is due to a defect or deficiency in a specific receptor found on platelets (component of blood that aids blood clot formation) called GPIb-IX-V. This particular receptor controls platelet adhesion, allowing them to ultimately form a clot and thereby prevent excessive bleeding.

Dr Elizabeth Gardiner and A/Prof Robert Andrews

Monash researchers from the Australian Centre of Blood Diseases in the Systems Haematology group, led by Associate Professor Robert Andrews and Dr Elizabeth Gardiner, and collaborators from the Alfred Hospital and the Kolling Institute of Medical Research (Sydney) have identified a new gene mutation in platelet receptor component GPIbβ in a patient with BSS. The patient had a greatly reduced number of platelets in the blood and a clinical history of mild bleeding.

Upon closer analysis of the patient’s platelets, a number of important platelet molecules were found to only be expressed at very low levels or were undetectable. Another molecule that assists with receptor organisation, called CD9, was also found to be reduced.

They discovered that this patient had a previously undescribed genetic mutation in GPIbβ that was interrupting the formation of important platelet receptors. This led to platelets that were unable to clot together properly, resulting in a longer bleeding time.

The link between mutated GPIbβ and reduced CD9 is unclear though has been previously reported in other BSS patients. As such, CD9 may be a new marker to help definitively diagnose BSS patients.

Reference: Qiao J, Davis AK, Morel-Kopp MC, Ward CM, Gardiner EE, Andrews R. Low levels of CD9 coincidental with a novel nonsense mutation in glycoprotein Ibβ in a patient with Bernard-Soulier syndrome.  Ann Hematol. 2015; 94(12): 2069-71

doi: 10.1007/s00277-015-2473-1