Summary
We have recently described a novel mutation screening technique for the diagnosis
of type 2B von Willebrand’s disease (vWD). Analysis involves the use of a synthetic
universal heteroduplex generator (UHG). To test the validity of the technique, we
have applied UHG screening to seven type 2B vWD patients of previously unknown genotype.
Characteristic heteroduplex patterns for Arg543Trp and Val553Met mutations were found
in three patients and one patient, respectively. A fifth patient gave a novel pattern
and direct sequencing revealed a hitherto unreported candidate mutation (Ser547Phe)
8 bases downstream of an “identifier” deletion in the UHG molecule. The two remaining
patients gave normal heteroduplex patterns; an Arg578Gln mutation was identified by
PstI digestion in one individual and no mutation could be identified in the sequence
covered by the UHG in the final patient. Using a combination of UHG technology and
restriction analysis, over 85% of type 2B vWD patients can be rapidly diagnosed by
genotype.
