Recurrent deletion in the human antithrombin III gene.
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.
Grundy
C B
CB
Charter Molecular Genetics Laboratory, Thrombosis Research Institute, Chelsea, London, UK.
Thomas
F
F
Millar
D S
DS
Krawczak
M
M
Melissari
E
E
Lindo
V
V
Moffat
E
E
Kakkar
V V
VV
Cooper
D N
DN
D000990:Antithrombin III / Q000235:genetics*; D020152:Antithrombin III Deficiency; D001483:Base Sequence; D015139:Blotting, Southern; D002872:Chromosome Deletion; D003062:Codon; D015342:DNA Probes; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013923:Thromboembolism / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics*
D003062:Codon; D015342:DNA Probes; D000990:Antithrombin III