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Severe prekallikrein deficiency associated with homozygosity for an Arg94Stop nonsense mutation
Author(s) -
Wynne Jones D.,
Russell Geoffrey,
Allford Sarah L.,
Burdon Kathryn,
Hawkins Gregory A.,
Bowden Donald W.,
Minaee Sophie,
Mumford Andrew D.
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05180.x
Subject(s) - prekallikrein , partial thromboplastin time , nonsense mutation , proband , allele , medicine , endocrinology , factor xii , coagulation , mutation , immunology , kallikrein , chemistry , biology , genetics , gene , biochemistry , missense mutation , enzyme
Summary 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.