Analysis of the genetic and phenotypic findings in Japanese patients with vascular-type Ehlers-Danlos syndrom

• Project/Area Number: 21591442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Dokkyo Medical University
• Principal Investigator: HATAMOCHI Atsushi 獨協医科大学, 医学部, 教授 (90172923)
• Co-Investigator(Renkei-kenkyūsha): SHIMAOKA Yayo 濁協医科大学, 医学部, 助教 (70528059) ; YAMAZAKI Soji 濁協医科大学, 医学部, 教授 (80008333) ; HAMA Naoto 濁協医科大学, 医学部, 講師 (70468346)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: エーラスダンロス症候群 / 血管型 / III型コラーゲン / COL3A1 / 遺伝子変異

Research Abstract

Vascular-type Ehlers-Danlos syndrome(vEDS) is a severe autosomal dominant inherited disorder resulting form mutations within theα1 typeIIIcollagen gene(COL3A1). Sequence analyses of the COL3A1 gene demonstrated heterozygous point mutations leading to glycine substitution in only nine patients(45%), while heterozygous splice-site mutations at the junction of the triple-helical exons were observed in the remaining 11 patients(55%). The average type III collagen production level in the cultured dermal fibroblasts was 14.6% of the normal value. The types of complication were not associated with specific mutations in COL3A1.

Research Products

• [Journal Article] 喀血と気胸を繰り返した血管型Ehlers-Danlos症候群(EDS)の1例 (2011)
  • Author(s): 松尾沙緒里, 横田雅史, 國井英治, 籏持淳
  • Journal Title: 臨床皮膚科 Volume: 65 Pages: 403-406
  • URL: http://www.dermatol.or.jp/
  • Peer Reviewed
• [Journal Article] Sigmoid colon perforation induced by the vascular type of Ehlers-Danlos Syndrome (2011)
  • Author(s): Omori H, Hatamochi A, Koike M, Sato Y, Kosho T, Kitakado Y, Oe T, Mukai T, Takubo K
  • Journal Title: Report of a Case. Surgery Today Volume: 41(5) Issue: 5 Pages: 733-736
  • DOI: 10.1007/s00595-010-4316-y
  • Peer Reviewed
• [Journal Article] 短期間に大腸穿孔性腹膜炎を2回起こした血管型Ehlers-Danlos症候群の1例 (2011)
  • Author(s): 緒方健一, 工藤啓介, 土居浩一, 大地哲史, 牧野公治, 籏持淳
  • Journal Title: 日本臨床外科学会雑誌 Volume: 72 Pages: 1882-1886
  • NAID: 10029613696
  • URL: http://ringe.jp/
  • Peer Reviewed
• [Journal Article] A response to:loss of dermatan-4-sulfotransferase 1(D4ST1/CHST14) function represents the first dermatan sulfate biosynthesis defect,"dermatan sulfate-deficient Adducted Thumb-Clubfoot Syndrome". Which name is appropriate,"Adducted Thumb-Clubfoot Syndrome (2011)
  • Author(s): Kosho T, Miyake N, Mizumoto S, Hatamochi A, Fukushima Y, Yamada S, Sugahara K, Matsumoto N
  • Journal Title: Hum Mutat Volume: 32 Issue: 12 Pages: 1507-1509
  • DOI: 10.1002/humu.21586
  • Peer Reviewed
• [Journal Article] Delineation of dermatan 4-O-sulfotransferase 1 deficient Ehlers-Danlos syndrome : observation of two additional patients and comprehensive review of 20 reported patients (2011)
  • Author(s): Shimizu K, Okamoto N, Miyake N, Taira K, Sato Y, Matsuda K, Akimaru N, Ohashi H, Wakui K, Fukushima Y, Matsumoto N, Kosho T
  • Journal Title: Am J Med Genet A Volume: 155A Issue: 8 Pages: 949-1958
  • DOI: 10.1002/ajmg.a.34115
  • Peer Reviewed
• [Journal Article] A response to : loss of dermatan-4-sulfotransferase 1 (D4ST1/CHST14) function represents the first dermatan sulfate biosynthesis defect, "dermatan sulfate-deficient Adducted Thumb-Clubfoot Syndrome". Which name is appropriate, "Adducted Thumb-Clubfoot Syndrome" or "Ehlers-Danlos syndrome"? (2011)
  • Author(s): Kosho T
  • Journal Title: Hum Mutat Volume: 32 Pages: 1507-1509
  • Peer Reviewed
• [Journal Article] Sigmoid colon perforation induced by the vascular type of Ehlers-Danlos Syndrome (2011)
  • Author(s): Omori H
  • Journal Title: Surgery Today Volume: 41 Pages: 733-736
  • Peer Reviewed
• [Journal Article] デルマタン4-O硫酸基転移酵素欠損に基づく新型エーラスダンロス症候群 (2011)
  • Author(s): 古庄知己
  • Journal Title: 日本小児科学会雑誌 Volume: 115 Pages: 1475-1475
  • Peer Reviewed
• [Journal Article] 診断のArtエーラスダンロス症候群の診断 (2011)
  • Author(s): 籏持淳
  • Journal Title: 西日本皮膚科 Volume: 73 Pages: 312-312
• [Journal Article] Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome (2010)
  • Author(s): Miyake N, Kosho T, Mizumoto S, Furuichi T, Hatamochi A, Nagashima Y, Arai E, Takahashi K, Kawamura R, Wakui K, Takahashi J, Kato H, Yasui H, Ishida T, Ohashi H, Nishimura G, Shiina M, Saitsu H, Tsurusaki Y, Doi H, Fukushima Y, Ikegawa S, Yamada S, Sugahar
  • Journal Title: Hum Mutat Volume: 31 Issue: 6 Pages: 1-9
  • DOI: 10.1002/ajmg.a.33498
  • Peer Reviewed
• [Journal Article] Pleuropulmonary pathology of vascular Ehlers-Danlos syndrome : spontaneous laceration, haematoma and fibrous nodules (2010)
  • Author(s): Kawabata Y, Watanabe A, Yamaguchi S, Aoshima M, Shiraki A, Hatamochi A, Kawamura T, Uchiyama T, Watanabe A, Fukuda Y
  • Journal Title: Histopathology Volume: 56 Pages: 944-950
  • Peer Reviewed
• [Journal Article] Clinical and genetic features of 20 Japanese patients with vascular-type Ehlers-Danlos syndrome (2010)
  • Author(s): Shimaoka Y, Kosho T, Wataya-Kaneda M, Funakoshi M, Suzuki T, Hayashi S, Mitsuhashi Y, Isei T, Aoki Y, Yamazaki K, Ono M, Makino K, Tanaka T, Kunii E, Hatamochi A
  • Journal Title: Br J Dermatol Volume: 163 Issue: 4 Pages: 704-710
  • DOI: 10.1111/j.1365-2133.2010.09874.x
  • Peer Reviewed
• [Journal Article] Ehlers-Danlos Syndrome Type IV, Vascular Type, Which Demonstrated a Novel Point Mutation in the COL3A1 Gene (2010)
  • Author(s): Sadakata R, Hatamochi A, Kodama K, Kaga A, Yamaguchi T, Soma T, Usui Y, Nagata M, Ohtake A, Hagiwara K, Kanazawa M
  • Journal Title: Intern Med Volume: 49 Pages: 1797-800
  • NAID: 130000299646
  • URL: http://dx.doi.org/10.2169/internalmedicine.49.3435
  • Peer Reviewed
• [Journal Article] A novel point mutation at donor splice-site in Intron 42 of type III collagen gene resulting in the inclusion of 30 nucleotides into the mature mRNA in a case of vascular type of Ehlers-Danlos syndrome (2010)
  • Author(s): Okita H, Ikeda Y, Mitsuhashi Y, Namikawa H, Kitamura Y, Hamasaki Y, Yamazaki S, Hatamochi A
  • Journal Title: Arch Dermatol Res Volume: 302 Issue: 5 Pages: 395-399
  • DOI: 10.1007/s00403-009-0970-6
  • Peer Reviewed
• [Journal Article] A novel point mutation at donor splice-site in Intron 42 of type III collagen gene resulting in the inclusion of 30 nucleotides into the mature mRNA in a case of vascular type of Ehlers-Danlos syndrome. (2010)
  • Author(s): Okita H
  • Journal Title: Arch Dermatol Res Volume: 302 Pages: 395-399
  • Peer Reviewed
• [Journal Article] Ehlers-Danlos Syndrome Type IV, Vascular Type, Which Demonstrated a Novel Point Mutation in the COL3A1 Gene. (2010)
  • Author(s): Sadakata R
  • Journal Title: INTERNAL MEDICINE Volume: 49 Pages: 1797-1800
  • Peer Reviewed
• [Journal Article] Clinical and genetic features of 20 Japanese patients with vascular-type Ehlers-Danlos syndrome. (2010)
  • Author(s): Shimaoka Y
  • Journal Title: Br J Dermatol Volume: 163 Pages: 704-710
  • Peer Reviewed
• [Journal Article] Pleuropulmonary pathology of vascular Ehlers-Danlos syndrome. (2010)
  • Author(s): Kawabata Y
  • Journal Title: spontaneous laceration, haematoma and fibrous nodules, Histopathology Volume: 56 Pages: 944-950
  • Peer Reviewed
• [Journal Article] 【遺伝子がかかわる皮膚疾患入門,責任遺伝子がはっきりした疾患】Ehlers-Danlos症侯群と遺伝子変異 (2010)
  • Author(s): 籏持淳
  • Journal Title: Dermatol Volume: 163 Pages: 67-76
• [Journal Article] Ehlers-Danlos syndrome with recurrent spontaneous pneumothoraces and cavitary lesion on chest X-ray as the initial complications (2009)
  • Author(s): Ishiguro T, Takayanagi N, Kawabata Y, Matsushima H, Yoshii Y, Harasawa K, Yamaguchi S, Yoneda K, Miyahara Y, Kagiyama N, Tokunaga D, Aoki F, Saito H, Kurashima K, Ubukata M, Yanagisawa T, Sugita Y, Okita H, Hatamochi A
  • Journal Title: Intern Med Volume: 48 Pages: 717-722
  • NAID: 130000122489
  • URL: http://dx.doi.org/10.2169/internalmedicine.48.1818
  • Peer Reviewed
• [Journal Article] 肺裂傷に伴う肺血腫が診断契機となったEhlers-Danlos症候群の1例 (2009)
  • Author(s): 松下文、高柳昇、石黒卓、原澤慶次、土屋典子、米田紘一郎、宮原庸介、山口昭三郎、矢野量三、徳永大道、斉藤大雄、倉島一喜、生方幹夫、柳沢勉、杉田裕、河端美則、沖田博、籏持淳
  • Journal Title: 日本呼吸器学会雑誌 Volume: 47 Pages: 704-710
  • NAID: 10026272035
  • URL: http://www.jrs.or.jp/
• [Journal Article] 肺裂傷に伴う肺血腫が診断契機となった Ehlers-Danlos 症候群の一例 (2009)
  • Author(s): 松下文
  • Journal Title: 日本呼吸器学会誌 47 Pages: 704-710
  • Peer Reviewed
• [Journal Article] Ehlers-Danlos Syndrome with Recurrent Spontaneous Pneumothoraces and Cavitary Lesion on Chest X-ray as the Initial Complicatioms (2009)
  • Author(s): Takashi Ishiguro
  • Journal Title: INTERNAL MEDICINE 48 Pages: 717-722
  • Peer Reviewed
• [Presentation] 血管型Ehlers-Danlos症候群の1例 (2011)
  • Author(s): 嶋岡弥生、林周次郎、濱崎洋一郎、籏持淳、照井慶太
  • Organizer: 第74回日本皮膚科学会栃木地方会
  • Place of Presentation: 壬生
  • Year and Date: 2011-09-29
• [Presentation] デルマタン4-0硫酸基転移酵素欠損に基づく新型工一ラスダンロス症候群 (2010)
  • Author(s): 古庄知己、三宅紀子、水本秀二、籏持淳、高橋淳、鳴海洋子、福嶋義光、菅原一幸、松本直通
  • Organizer: 第55回日本人類遺伝学会
  • Place of Presentation: 埼玉
  • Year and Date: 2010-10-27
• [Presentation] 診断のArt : Ehlers-Danlos症候群 (2010)
  • Author(s): 籏持淳
  • Organizer: 第62回日本皮膚科学会西部支部大会
  • Place of Presentation: 倉敷
  • Year and Date: 2010-10-24
• [Presentation] 血管型工一ラスダンロス症候群の1例 (2010)
  • Author(s): 牧野公治、サ浩信、緒方健一、籏持淳
  • Organizer: 第109回日本皮膚科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-04-16
• [Presentation] 多発関節弛緩型Ehlers-Danlos症候群(EDS)の1例 (2010)
  • Author(s): 嶋岡弥生、籏持淳、菅野美紀、濱崎洋一郎、山崎讐次、船越美由紀、橋本隆、芳野信、PeterH. Byers
  • Organizer: 第109回日本皮膚科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-04-16
• [Presentation] 多発関節弛緩型Ehlers-Danlos症侯群(EDS)の1例 (2010)
  • Author(s): 嶋岡弥生
  • Organizer: 第109回日本皮膚科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-04-16
• [Presentation] 血管型エーラスダンロス症候群の1例 (2010)
  • Author(s): 牧野公治
  • Organizer: 第109回日本皮膚科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-04-16
• [Presentation] Clinical and genetic features of Japanese patients with the vascular-type of Ehlers-Danlos syndrome (2010)
  • Author(s): Hatamochi A
  • Organizer: 9th Congress of the German-Japanese Society of Dermatology
  • Place of Presentation: Weimar, Germany
• [Presentation] A Japanese patient with Arthrochalasia-type Ehlers-Danlos syndrome (2010)
  • Author(s): Koyano S, Hatamochi A, YoshinoM, Hashimoto T, Byers PH
  • Organizer: 9th Congress of the German-Japanese Society of Dermatology
  • Place of Presentation: Weimar, Germany
• [Presentation] 難治性疾患克服研究事業による血管型工一ラスダンロス症候群の実態調査 (2010)
  • Author(s): 古庄知己、籏持淳、渡邉淳、森崎裕子、福嶋義光
  • Organizer: 第34回日本遺伝カウンセリング学会
  • Place of Presentation: 東京
• [Presentation] Sigmoid colon perforation induced by the vascular type of Ehlers-Danlos Syndrome (2010)
  • Author(s): Shimaoka Y
  • Organizer: 9^<th> Congress of the German-Japanese Society of Dermatology
  • Place of Presentation: Weimar, Germany
• [Presentation] A Japanese patient with Arthrochalasia-type Ehlers-Danlos syndrome. (2010)
  • Author(s): Koyano S
  • Organizer: 9^<th> Congress of the German-Japanese Society of Dermatology
  • Place of Presentation: Weimar, Germany
• [Presentation] Clinical and genetic features of Japanese patients with the vascular-type of Ehlers-Danlos syndrome. (2010)
  • Author(s): Hatamochi A
  • Organizer: 9^<th> Congress of the German-Japanese Society of Dermatology
  • Place of Presentation: Weimar, Germany
• [Presentation] S状結腸穿孔を生じた血管型工一ラスダンロス症候群(EDS)の1例 (2009)
  • Author(s): 嶋岡弥生、籏持淳、濱崎洋一郎、山崎讐次、船越美由紀、管野美紀、大森浩志
  • Organizer: 第73回日本皮膚科学会東部支部学術大会
  • Place of Presentation: 甲府
  • Year and Date: 2009-09-26
• [Presentation] S状結腸穿孔を生じた血管型エーラスダンロス症候群(EDS)の1例 (2009)
  • Author(s): 嶋岡弥生
  • Organizer: 第73回日本皮膚科学会 東部支部学術大会
  • Place of Presentation: 甲府富士屋ホテル
  • Year and Date: 2009-09-26
• [Book] Ehlers-Danlos症候群.皮膚疾患診療実践ガイド (2011)
  • Author(s): 籏持淳
  • Publisher: 文光堂東京
• [Book] その他の皮膚形成異常.皮膚疾患診療実践ガイド (2011)
  • Author(s): 籏持淳
  • Publisher: 文光堂東京
• [Book] Marfan症候群.今日の皮膚疾患治療指針 (2011)
  • Author(s): 籏持淳
  • Total Pages: 545
  • Publisher: 医学書院東京
• [Book] その他の皮膚形成異常症.今日の皮膚疾患治療指針 (2011)
  • Author(s): 籏持淳
  • Publisher: 医学書院東京
• [Book] 皮膚形成異常症の遺伝相談.今日の皮膚疾患治療指針 (2011)
  • Author(s): 籏持淳
  • Publisher: 医学書院東京
• [Book] 皮膚疾患診療実践ガイド(Ehlers-Danlos症候群) (2011)
  • Author(s): 籏持淳
  • Publisher: 文光堂
• [Book] 皮膚疾患診療実践ガイド(その他の皮膚形成異常) (2011)
  • Author(s): 籏持淳
  • Publisher: 文光堂
• [Book] 今日の皮膚疾患治療指針(Marfan症候群) (2011)
  • Author(s): 籏持淳
  • Publisher: 医学書院
• [Book] 今日の皮膚疾患治療指針(その他の皮膚形成異常症) (2011)
  • Author(s): 籏持淳
  • Publisher: 医学書院
• [Book] 今日の皮膚疾患治療指針(皮膚形成異常症の遺伝相談) (2011)
  • Author(s): 籏持淳
  • Publisher: 医学書院
• [Book] Ehlers-Danlos症候群.小児科臨床ピクシス年代別子どもの皮膚疾患 (2010)
  • Author(s): 籏持淳
  • Publisher: 中山書店東京