title: A complex genomic abnormality found in a patient with antithrombin deficiency and autoimmune disease-like symptoms.
abstract: Hereditary antithrombin (AT) deficiency is an autosomal dominant thrombophilic disorder caused by SERPINC1 abnormality. In the present study, we analyzed SERPINC1 in a Japanese patient with AT deficiency and autoimmune disease-like symptoms. Direct sequencing and multiplex ligation-dependent probe amplification revealed that the patient was hemizygous for the entire SERPINC1 deletion. Single nucleotide polymorphism genotyping, gene dose measurement, and long-range polymerase chain reaction (PCR) followed by mapping PCR and direct sequencing of the long-range PCR products revealed that the patient had an approximately 111-kb gene deletion from exon 2 of ZBTB37 to intron 5 of RC3H1, including the entire SERPINC1 in chromosome 1. We also found a 7-bp insertion of an unknown origin in the breakpoint, which may be a combination of three parts with a few base-pair microhomologies, resulting from a replication-based process known as 'fork stalling and template switching'. Because RC3H1, which encodes the protein roquin is involved in the repression of self-immune responses, the autoimmune disease-like symptoms of the patient may have resulted from this gene defect. In conclusion, we identified an entire SERPINC1 deletion together with a large deletion of RC3H1 in an AT-deficient patient with autoimmune disease-like symptoms.
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, 1-1-20 Daiko-Minami, Higashi-ku, Nagoya, 461-8673, Japan.
authors.forename: Io
authors.initials: I
authors.lastname: Kato
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takagi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ando
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Moe
authors.initials: M
authors.lastname: Murata
authors.forename: Akira
authors.initials: A
authors.lastname: Takagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Murate
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Nakashima
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Kojima
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000235:genetics*; D020152:Antithrombin III Deficiency / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D005091:Exons; D005260:Female; D018628:Gene Dosage; D057898:Hemizygote; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics*; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C000592051:RC3H1 protein, human; D016601:RNA-Binding Proteins; C542513:SERPINC1 protein, human; D000990:Antithrombin III; D044767:Ubiquitin-Protein Ligases