title: A frameshift mutation leading to type 1 antithrombin deficiency and thrombosis.
abstract: Type 1 antithrombin III (ATIII) deficiency, which is the commonest form of inherited ATIII defect, is characterized by a quantitative reduction in both immunologically and functionally detectable protein. This condition is associated with a high incidence of thromboembolic disorder. Previous investigations have shown that the ATIII genes in the majority of cases are grossly intact, but the precise underlying molecular defects remain unknown. We have investigated the molecular basis of a type 1 ATIII deficiency in an Italian kindred by enzymatic amplification of the ATIII gene sequences in affected family members and direct sequencing of the amplified genomic DNA. A novel mutation, the deletion of a single T in the second position of codon 119, was identified in each of the affected individuals. The resulting frameshift leads to a premature termination in codon 126, effectively resulting in a null allele.
authors.affiliation: MRC Molecular Haematology, John Radcliffe Hospital, Oxford, England.
authors.forename: R J
authors.initials: RJ
authors.lastname: Olds
authors.forename: D A
authors.initials: DA
authors.lastname: Lane
authors.forename: G
authors.initials: G
authors.lastname: Finazzi
authors.forename: T
authors.initials: T
authors.lastname: Barbui
authors.forename: S L
authors.initials: SL
authors.lastname: Thein
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000990:Antithrombin III / Q000235:genetics; D020152:Antithrombin III Deficiency; D001483:Base Sequence; D015252:Deoxyribonucleases, Type II Site-Specific; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013927:Thrombosis / Q000235:genetics*
chemical_list: D000990:Antithrombin III; C024388:CTGCAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific