Structural integrity of the glycoprotein IIb and IIIa genes in Glanzmann
thrombasthenia patients from Israel
ME Russell, U Seligsohn, BS Coller, MH Ginsberg, P Skoglund and T Quertermous
Cardiac Unit, Massachusetts General Hospital, Boston 02114.
Glanzmann thrombasthenia is an autosomal recessive disorder of the platelet
glycoproteins (GP) IIb and IIIa. These glycoproteins normally serve as
receptors for other adhesive glycoproteins, including fibrinogen, von
Willebrand factor, and fibronectin. Most patients affected by Glanzmann
thrombasthenia have low levels of GPIIb and GPIIIa; however, the separate
mechanisms responsible for the deficiency in each remain to be determined.
cDNA clones coding for the GPIIb and GPIIIa have been recently isolated,
and their corresponding genomic sequences have been colocalized to the long
arm of chromosome 17. Since a deletional event involving one or both of
these structural genes could explain the disease phenotype, we have studied
the DNA of two previously well-characterized cohorts of Glanzmann
thrombasthenia patients from Israel. We performed Southern analysis with
near full- length cDNA probes on genomic DNA obtained from 20 individuals.
Four restriction enzyme digests were completed on each DNA sample. The
similarity of banding patterns among probands, family members, and controls
indicated that there were no major insertions or deletions in either the
GPIIb or GPIIIa genes. Thus, the genetic defect in these patients with
Glanzmann thrombasthenia is most likely due to either a small change in the
nucleotide sequence of the coding region or a defect in the regulatory
region of one or both genes.
Volume 72,
Issue 5,
pp. 1833-1836,
11/01/1988
Copyright © 1988 by The American Society of Hematology
