Blood Journal
Leading the way in experimental and clinical research in hematology

Recurrent deletion in the human antithrombin III gene

  1. CB Grundy,
  2. F Thomas,
  3. DS Millar,
  4. M Krawczak,
  5. E Melissari,
  6. V Lindo,
  7. E Moffat,
  8. VV Kakkar, and
  9. DN Cooper
  1. Charter Molecular Genetics Laboratory, Thrombosis Research Institute, Chelsea, London, UK.


Eight unrelated patients with recurrent thromboembolism, a family history of thrombosis, and plasma antithrombin III (ATIII) activity/antigen levels consistent with a diagnosis of heterozygous type I ATIII deficiency were studied by polymerase chain reaction/direct sequencing of ATIII gene exon-coding regions. Frameshift mutations of one base and two bases, respectively, were found to have occurred in two unrelated patients at the same GAG codon (Glu 245) within exon 4 of the ATIII gene. A literature search showed six further hitherto unrecognized deletion “hotspots” in four other human genes. These deletion-prone sites exhibited sufficient sequence homology with each other to derive a consensus sequence (T G A/G A/G G A/C), suggesting that deletion in human genes may not only be non- random but also sequence-directed.