Severe bleeding tendency in a patient with Bernard-Soulier syndrome associated with a homozygous single base pair deletion in the gene coding for the human platelet glycoprotein Ibalpha.

PURPOSE

The genetic basis of Bernard-Soulier syndrome (BSS) was studied to clarify a relationship between severe clinical manifestations and gene abnormality.

PATIENT AND METHODS

A patient with BSS had a severe bleeding tendency that was sometimes life threatening. Flow cytometric analysis of the patient's and normal control platelets was performed to study which glycoprotein (GP) was impaired in glycoprotein Ib/V/IX complex. The genes encoding GPIbalpha from the patient's and control genomic DNA were amplified and directly sequenced.

RESULTS

Flow cytometric analysis revealed a defect of GPIbalpha on the surface of the patient's platelets. A homozygous single base pair deletion was identified in seven repeats of adenine at positions 1932 to 1938 in the GPIbalpha gene. This mutation, which has been previously reported, results in a frameshift and predicts a premature stop codon leading to a truncated peptide that cannot fix on the platelet membrane.

CONCLUSION

This patient's severe clinical phenotype would be explained by this mutation in the GPIbalpha gene.