Severe prekallikrein deficiency associated with homozygosity for an Arg94Stop nonsense mutation

Abstract

An elderly patient with no abnormal bleeding presented with prolongation of the activated partial thromboplastin time (aPTT). Preincubation of plasma with aPTT reagent caused shortening of the abnormal clotting time. Plasma prekallikrein (PK) activity and antigen were <5 u/dL. Molecular analysis showed a homozygous Arg94Stop substitution in the PK gene, predicted to prevent expression of the mutant allele. The five heterozygous offspring of the proband each showed a normal aPTT but reduced PK activity and antigen. This is the first description of a kindred in which absence of expression of one or both PK alleles has been confirmed by genotype.