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.
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Acknowledgments
We would like to thank C. Wakamatsu for her expert technical assistance. This study was supported in part by grants-in-aid from the Baxter Coagulation Research Foundation (I.K.); the Japanese Ministry of Education, Culture, Sports, Science, and Technology (25293129: T.K. and 25460683: A.T.); and the Japanese Ministry of Health, Labour and Welfare (Research on Measures for Intractable Diseases: TK). The authors would like to thank Enago for the English language review.
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The authors declare that they have no conflict of interest.
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Kato, I., Takagi, Y., Ando, Y. et al. A complex genomic abnormality found in a patient with antithrombin deficiency and autoimmune disease-like symptoms. Int J Hematol 100, 200–205 (2014). https://doi.org/10.1007/s12185-014-1596-9
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DOI: https://doi.org/10.1007/s12185-014-1596-9