Severe type III von Willebrand's disease caused by deletion of exon 42 of
the von Willebrand factor gene: family studies that identify carriers of
the condition and a compound heterozygous individual
IR Peake, MB Liddell, P Moodie, G Standen, DJ Mancuso, EA Tuley, LA Westfield, JM Sorace, JE Sadler and CL Verweij
Department of Haematology, University of Wales College of Medicine,
Cardiff, UK.
Southern blotting was performed with cDNA probes for the human von
Willebrand factor (vWF) gene on six patients with severe type III von
Willebrand's disease (vWD). A partial deletion in the 3' end of the vWF
gene was demonstrated in one individual whose parents were related and who
had an alloantibody inhibitor to vWF. A resulting novel 2.0- kilobase (kb)
EcoRI fragment was used for carrier detection within the patient's family,
and seven carriers of this recessive trait were identified. Of the six
tested, five had normal or only slightly reduced levels of vWF antigen, but
with generally higher levels of factor VIII. The sixth carrier had
moderately severe vWD and it is proposed that this patient is heterozygous
for the defective vWF gene and a second recessive vWF defect. The novel
2.0-kb EcoRI restriction fragment was cloned and sequenced, and compared
with that of the corresponding normal 4.2-kb EcoRI fragment that includes
exons 41 and 42 of the vWF gene. A deletion of 2,320 base pairs (bp) which
included exon 42, was identified and a novel 182-bp insert was found
between the breakpoints. This insert was detected by polymerase chain
reaction amplification both in the patient's DNA and in his carrier
relatives.
Volume 75,
Issue 3,
pp. 654-661,
02/01/1990
Copyright © 1990 by The American Society of Hematology
