title: Causative genetic mutations for antithrombin deficiency and their clinical background among Japanese patients.
abstract: We summarize causative genetic mutations for antithrombin (AT) deficiency and their clinical background in Japanese patients. A total of 19 mutations, including seven novel mutations, were identified. We also summarize clinical symptoms of thrombosis, age at onset, family history, and contributing factors for thrombosis, and review the use of prophylactic anticoagulation in pregnant women with heterozygous type II heparin binding site defects (HBS) AT deficiency. The prevalence of thrombosis in probands with type I AT deficiency (88%) was double that observed in those with type II AT deficiency (50%). The prevalence of thrombotic episodes among family members was also higher for type I AT deficiency subjects (82%) than for those with type II AT deficiency (0%). The most common contributing factor for thrombosis among women with type I AT deficiency was pregnancy. Forty-five percent of women with type I AT deficiency developed thrombotic events before the 20th week of gestation. In contrast, women with type II (HBS) AT deficiency appear to be at a lower risk of thrombosis during pregnancy. In conclusion, thrombotic risk varies among different subtypes. Risk assessments based on genetic/clinical backgrounds may contribute to appropriate diagnosis, treatment, and prophylaxis for patients with AT deficiency.
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Akiko
authors.identifier: http://orcid.org/0000-0001-6076-6778
authors.initials: A
authors.lastname: Sekiya
authors.affiliation: Department of Central Clinical Laboratory, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.
authors.forename: Fumina
authors.initials: F
authors.lastname: Taniguchi
authors.affiliation: Department of Central Clinical Laboratory, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamaguchi
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kamijima
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Shonosuke
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Katsu
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Hanamura
authors.affiliation: Department of Central Clinical Pathology, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Takata
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Department of Internal Medicine (III), Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
authors.forename: Hidesaku
authors.initials: H
authors.lastname: Asakura
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohtake
authors.affiliation: Division of Health Sciences, Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, Ishikawa, 920-0942, Japan. eriko86@staff.kanazawa-u.ac.jp.
authors.forename: Eriko
authors.initials: E
authors.lastname: Morishita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058833:Antithrombin Proteins / Q000172:deficiency* / Q000235:genetics; D044466:Asian People; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000175:diagnosis; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications / Q000175:diagnosis; D013927:Thrombosis / Q000209:etiology
chemical_list: D058833:Antithrombin Proteins
keywords: Antithrombin deficiency; Genetic analysis; Heparin binding site