Severe prekallikrein deficiency due to a homozygous Trp499Stop nonsense mutation

Abstract

Prekallikrein deficiency is a rare autosomal recessive disease not considered to be associated with a tendency for bleeding, despite marked prolongation of activated partial thromboplastin time. Currently, six kinds of mutations in the prekallikrein gene are known to be associated with prekallikrein deficiency. In this report, we describe a patient with idiopathic thrombocytopenic purpura who was recognized to have severe prekallikrein deficiency. Molecular analysis of the patient's prekallikrein gene showed a homozygous Trp499Stop nonsense mutation that has not been reported previously. The mutant allele is predicted to encode a truncated protein lacking half of the catalytic domain of prekallikrein, suggesting that the truncated protein causes prekallikrein deficiency in the patient.

A structure–function analysis in patients with prekallikrein deficiency

“…A total of 12 families with a total of 20 patients were gathered [8][9][10][11][12][13][14][15][16][17][18]. The main features of these families are reported in Table 1.…”

Prekallikrein Deficiency Presenting as Recurrent Cerebrovascular Accident: Case Report and Review of the Literature

“…Chromosomal localization of the gene has been mapped to the q34-q35 region on the long arm of chromosome 4, encoded by a single gene ( KLKB1 ), and composed of 15 exons and 14 introns [8]. Seven types of mutations in prekallikrein deficient families have been identified by molecular genetic analysis, with most mutations being found in the light chain region of the prekallikrein gene [9]. …”

Diagnostic Pearls and Clinical Implications of Prekallikrein Deficiency

“…In 1973, Wuepper et al showed that the "Fletcher factor" was actually PK [4]. It is an autosomal recessive disorder with more than seven different types of mutation identified by molecular genetic analysis [5]. PK deficiency has been classified as type I and type II based on the level of activity and antigen.…”