Evidence for Genetic Homogeneity in a Familial Platelet Disorder With Predisposition to Acute Myelogenous Leukemia (FPD/AML)

15, 1998 issue of Blood.2,3 Both of them affect Arg306, an important APC cleavage site.The first one is a new factor V mutation associated with APC resistance (factor V Cambridge, G1091 = C mutation, Arg306 = Thr substitution).This mutation was found in a family with a strong history of thrombosis.Our group has independently described another novel mutation (A1090 = G) that results in Arg306 = Gly substitution but it is, however, not associated with APC resistance. 2 The mutation was found in both thrombotic and nonthrombotic subjects.Although both new mutations affect similarly the Arg306 cleavage site, only the Arg306 = Thr substitution results in both APC resistance and increased risk of thrombosis.The clinical significance of Arg306 = Gly substitution remains uncertain.Our group has studied further the prevalence of the Arg306 = Gly substitution in Hong Kong Chinese.High-molecular-weight DNA was extracted from the blood samples obtained from 89 healthy blood donors and 260 diabetic patients.The mutation is detected by a restriction enzyme digest of the amplified exon 7 of factor V gene with BstNI (New England Biolabs, Beverly, MA), which has a restriction site of CC ٌ AGG.The DNA fragments were studied by 6% polyacrylamide gel electrophoresis.The undigested DNA fragment was a 240-bp polymerase chain reaction product.A complete digestion of this 240-bp DNA fragment with BstNI was expected to yield two shorter fragments of 100 and 140 bp in length.The presence of an A1090 = G mutation resulted in the loss of the cleavage site for BstNI.3 The mutation was found in 4 of the 89 (4.5%) healthy blood donors and 8 of the 260 (3.1%) diabetic subjects.There is no statistically significant difference between these two figures and the incidence rate of 2 of 43 (4.7%) previously reported in thrombotic patients.3 It appears that there is a difference in the APC capacity to cleave Thr306 and Gly306.Thr306 seems to confer APC resistance to the factor V molecule.On the other hand, susceptibility to APC cleavage appears to persist for Gly306.Although, like Arg 306 = Thr, the Arg306 = Gly substitution affects similarly the Arg306 APC cleavage site of factor V gene, Arg306 = Gly may not have any clinical significance.The current data do not suggest that it predisposes to clinical thrombosis.