We present a patient with
Bernard-Soulier syndrome harboring a novel mutation. Flow cytometric analysis showed that the
glycoprotein (GP) Ib/IX complex was absent from the platelet surface. By immunoblotting, GPIbalpha, GPIbbeta and GPIX were not detected in the platelet lysates.
Glycocalicin, the soluble GPIbalpha fragment, was also absent in the plasma. Genetic analysis revealed a novel homozygous 8-base pair deletion in the GPIbalpha gene, 1136_1143delTTCACATG, which was predicted to cause a frame shift and the addition of 13 altered
amino acids followed by premature termination. No mutation was found in the coding sequence of the GPIbbeta or GPIX genes. We demonstrated that the novel deletion mutation resulted in complete defectiveness of the GPIbalpha
protein and null expression of the entire GPIb/IX complex, and was responsible for the
Bernard-Soulier syndrome phenotype in this patient. Although the presence of a truncated GPIbalpha
protein has been often documented, complete absence of the
protein has been scarcely reported in
Bernard-Soulier syndrome patients with a GPIbalpha mutation causing a
premature stop codon. An underlying molecular mechanism to explain how the synthesis of a truncated
protein is inhibited in selected cases remains to be elucidated.