Molecular defects of platelets in Bernard-Soulier syndrome.

In 1969, it was shown that platelets of patients with Bernard-Soulier (B-S) syndrome exhibited an altered electrophoretic mobility arising from a surface membrane sialic acid deficiency. Subsequent studies showed that a major membrane glycoprotein, GP Ib, was either deleted, reduced in concentration, or structurally modified in B-S platelets. Controversy persists, however, as to the specificity of the defect in platelets of different patients, especially with regard to studies performed on patients in different laboratories. We have now studied platelets from six patients, and during these studies have analyzed the platelet proteins and glycoproteins by single and two-dimensional SDS-PAGE or by crossed immunoelectrophoresis. The surface proteins of the platelets of different patients have been radiolabelled with 3H or 125I. Our studies point to the deletion or severe reduction in concentration of GPIb alpha and Ib beta in the platelets of five patients, detectable but reduced levels of Ib were present in the platelets of the other patient. Studies using 3H-labelled glycoproteins suggest that mol.wt. 82,000 (GP V) and mol.wt. 17,000 glycoproteins are also missing or abnormal. The relationship between these additional defects and the major GP Ib lesion remains to be determined. It should be emphasized that these are membrane abnormalities, no alpha-granule or cyto-plasmic protein deficiencies have been located in B-S platelets.