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The molecular genetic basis of Glanzmann's thrombasthenia in a gypsy
population in France: identification of a new mutation on the alpha IIb
gene
N Schlegel, O Gayet, MC Morel-Kopp, B Wyler, MF Hurtaud-Roux, C Kaplan and J Mc Gregor
Service d'Hematologie Biologique, Hopital Robert Debre, Paris, France.
Glanzmann's thrombasthenia is a rare inherited bleeding disorder caused by
a qualitative or quantitative defect of platelet alpha IIb beta 3. We
describe here a new mutation that is the molecular genetic basis of
Glanzmann's thrombasthenia in two gypsy families. Our investigation was
focused on the alpha IIb gene as a result of biochemical and immunologic
analysis of patients' platelets showing undetectable alpha IIb but residual
beta 3 levels. The entire alpha IIb cDNA was polymerase chain reaction
(PCR) amplified using patients platelet RNA. Sequence analysis showed an
8-bp deletion located at the 3' end of exon 15. This deletion causes a
reading-frame shift leading to a premature stop codon and the synthesis of
a severely truncated form of alpha IIb. Genomic DNA study showed a G-->A
substitution, the Gypsy mutation, at the splice donor site of intron 15.
This mutation results in an abnormal splicing occurring at an alternative
donor site located 8 bp upstream from the mutation. Based on those results,
an allele-specific PCR analysis was developed to allow a rapid
identification of the mutation in patients and potential carriers of the
gypsy community. This PCR analysis can also be used for genetic counseling
and antenatal diagnosis.
Volume 86,
Issue 3,
pp. 977-982,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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