title: Recurrent deletion in the human antithrombin III gene.
abstract: 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.
authors.affiliation: Charter Molecular Genetics Laboratory, Thrombosis Research Institute, Chelsea, London, UK.
authors.forename: C B
authors.initials: CB
authors.lastname: Grundy
authors.forename: F
authors.initials: F
authors.lastname: Thomas
authors.forename: D S
authors.initials: DS
authors.lastname: Millar
authors.forename: M
authors.initials: M
authors.lastname: Krawczak
authors.forename: E
authors.initials: E
authors.lastname: Melissari
authors.forename: V
authors.initials: V
authors.lastname: Lindo
authors.forename: E
authors.initials: E
authors.lastname: Moffat
authors.forename: V V
authors.initials: VV
authors.lastname: Kakkar
authors.forename: D N
authors.initials: DN
authors.lastname: Cooper
mesh_terms: 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*
chemical_list: D003062:Codon; D015342:DNA Probes; D000990:Antithrombin III