title: De novo splice site mutation in the antithrombin III (AT3) gene causing recurrent venous thrombosis: demonstration of exon skipping by ectopic transcript analysis.
abstract: A single basepair substitution at conserved position -1 in the exon 3a donor splice site of the liver-expressed antithrombin III (AT3) gene was detected by PCR/direct sequencing in a patient with sporadic type 1 ATIII deficiency and recurrent venous thrombosis. The lesion, a heterozygous silent AAG----AAA transition at Lys 176 occurred de novo in the proposita. Ectopic transcript analysis of lymphocyte mRNA demonstrated the presence of an abnormally sized mRNA specific to the patient which was shown by cDNA sequencing to lack exon 3a. Oligonucleotide discriminant hybridization demonstrated the absence of any detectable transcript of normal length derived from the disease allele. These findings demonstrate the utility of ectopic transcript analysis in the characterization of defects of mRNA splicing.
authors.affiliation: Charter Molecular Genetics Laboratory, Thrombosis Research Institute, London, United Kingdom.
authors.forename: L P
authors.initials: LP
authors.lastname: Berg
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: P J
authors.initials: PJ
authors.lastname: Green
authors.forename: R
authors.initials: R
authors.lastname: Slomski
authors.forename: J
authors.initials: J
authors.lastname: Reiss
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*; D001483:Base Sequence; D005091:Exons; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012008:Recurrence; D013924:Thrombophlebitis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000990:Antithrombin III