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


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.


CONCLUSIONS
This patient's severe clinical phenotype would be explained by this mutation in the GPIbalpha gene.
Mitsui
T
T
Department of Pediatrics, Yamagata University, School of Medicine, Japan.
Yokoyama
S
S
Yazaki
N
N
Hayashi
T
T
Suzuki
K
K
Shimizu
Y
Y
Kawakami
T
T
Kanazawa
C
C
Katsuura
M
M
Ikegami
T
T
Hayasaka
K
K
D000293:Adolescent; D001483:Base Sequence; D001606:Bernard-Soulier Syndrome / Q000150:complications / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D006470:Hemorrhage / Q000150:complications / Q000235:genetics*; D006801:Humans; D010375:Pedigree; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013921:Thrombocytopenia / Q000150:complications
D017931:DNA Primers; D019038:Platelet Glycoprotein GPIb-IX Complex