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CN Finch, JL Miller, VA Lyle and RI Handin
Department of Pathology, SUNY Health Science Center, Syracuse 13210.
The underlying molecular basis for Bernard-Soulier Disease (BSD) is
currently unknown. Platelets from patients with this autosomal recessive
bleeding disorder have multiple abnormalities, including a markedly reduced
von Willebrand factor-dependent adhesiveness due to a deficiency of the
platelet membrane glycoprotein (GP) Ib/IX complex. In the present studies,
we have used an intragenic restriction fragment length polymorphism (RFLP)
for Taq I in the GPIb alpha gene to study linkage between this gene and the
inheritance of BSD in a family with two affected siblings. Whereas the
proband was heterozygous, showing both the 0.7 and 4.0 kb bands of this
polymorphism (A/B), her affected brother was homozygous for the 0.7 kb band
(A/A). Accordingly, these siblings did not inherit the same pair of GPIb
alpha alleles from their parents. Additionally, one child of the proband
was A/A, while the second studied child was A/B, with neither showing any
evidence of BSD. No construct of heterozygosity or homozygosity for GPIb
alpha alleles in this family is consistent with a model in which one or
more defective GPIb alpha alleles could produce BSD. RFLP analysis with
BamHI or HindIII showed entirely normal patterns in the patients,
indicating the absence of any gross deletion of the GPIb alpha gene. GPIb
alpha mRNA from patient platelets was reverse transcribed and subsequently
amplified by the polymerase chain reaction, demonstrating the presence of
GPIb alpha transcript. Furthermore, trace amounts of GPIb could be shown on
the surface of patient platelets. Based on these results, a defect in the
GPIb alpha gene is unlikely to be the cause of BSD in this family.
This article has been cited by other articles:
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| Copyright © 1990 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
