A de novo and heterozygous gene deletion causing a variant of von
Willebrand disease
F Bernardi, G Marchetti, S Guerra, A Casonato, D Gemmati, P Patracchini, G Ballerini and F Conconi
Centro Studi Biochimici delle Patologie del Genoma Umano-Istituto di
Chimica Biologica, Universita di Ferrara, Italy.
An abnormal von Willebrand factor (vWF) gene restriction pattern has been
found in a patient with von Willebrand disease. Because this gene
alteration is not present in his parents or in 50 normal and 25 affected
subjects, and the restriction fragment length polymorphism haplotypes are
inherited normally in the patient's family, we suggest that a de novo
mutation is present. Bands with reduced intensity and additional fragments,
observed in several restriction digests, hybridize with noncontiguous copy
DNA (cDNA) portions, thus indicating the presence of a heterozygous gene
deletion. The deletion removes a genomic region containing at least codons
1147 through 1854 and corresponding to the D3-A3 homologous protein
domains. The extent of the vWF pseudogene on chromosome 22 is roughly
similar to that of the deleted area. However, the pseudogenic nature of the
deletion is excluded by the mapping of bands with reduced intensity in the
patient to the true vWF gene. The vWF antigen levels are one fourth of
normal and ristocetin cofactor activity is severely impaired. The reduction
of high molecular weight multimers in plasma and platelets and the altered
triplet morphology are compatible with the presence of a dominant variant
of type II von Willebrand disease.
Volume 75,
Issue 3,
pp. 677-683,
02/01/1990
Copyright © 1990 by The American Society of Hematology
