Bernard‐Soulier syndrome Karlstad: Trp 498→Stop mutation resulting in a truncated glycoprotein Ibα that contains part of the transmembranous domain

• Published in: British journal of haematology Vol. 98; no. 1; pp. 57 - 63
• Main Authors: Holmberg, Lars, Karpman, Diana, Nilsson, Ingmar, Olofsson, Tor
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.1997; Blackwell
• Subjects: Aged; Bernard-Soulier Syndrome - genetics; Bernard‐Soulier syndrome; Biological and medical sciences; bleeding disorder; Blood Platelets - physiology; Blotting, Western; Flow Cytometry; giant platelets; glycoprotein Ibα; Hematologic and hematopoietic diseases; Humans; Male; Medical sciences; Mutation; Platelet diseases and coagulopathies; Platelet Glycoprotein GPIb-IX Complex - genetics; Sequence Analysis, DNA; stop codon; Human; Transmembrane protein; Bernard Soulier disease; Exploration; Male; Hemopathy; Glycoproteins; Genetic disease; Giant cell; Case study; Platelet; Etiology; Molecular complex; Receptor protein; Molecular biology; Willebrand factor; Coagulation factor; Biological receptor
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1997.1772993.x

In Bernard‐Soulier syndrome, a hereditary bleeding disorder, the platelets are deficient in the glycoprotein (GP) Ib–IX–V complex, a major receptor for the von Willebrand factor. The components of the complex are encoded by separate genes. Patients with this syndrome have a variable expression level of the receptor protein on platelets depending on the specific genetic abnormality. We describe a patient with life‐long bleeding symptoms, who is homozygous for a unique stop mutation, Trp 498→ Stop in the GPIbα gene, resulting in a truncated GPIbα polypeptide chain. In contrast to previously reported truncated forms of GPIbα, this form contains a portion of the transmembranous domain as well as the juxtamembranous cysteines engaged in a disulphide bond with GPIbβ. Flow cytometry with GPIbα antibodies demonstrated the presence of GPIb on the patient’s platelets, although in reduced amounts compared to normal controls. GPIX was similarly detectable. Immunoblotting demonstrated that the patient synthesized a truncated GPIbα of the expected size of 130 K, which was, however, sensitive to proteolysis. These studies show that GPIbα lacking the intracytoplasmic tail can be expressed at the platelet surface provided elements of the transmembranous domain are present.