Disease gene identification of a new type of Ehlers-Danlos syndrome

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790341
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Human genetics
• Research Institution: Yokohama City University
• Principal Investigator: MIYAKE Noriko Yokohama City University, 医学部, 准教授 (40523494)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Naomichi 横浜市立大学, 医学研究科, 教授 (80325638) ; KOSHO Tomoki 信州大学, 医学部, 講師 (90276311)
• Project Period (FY): 2009 – 2010
• Keywords: 分子遺伝学 / 単一遺伝子疾患

Research Abstract

We identified CHST14 as a disease gene for the novel autosomal recessive Ehlers-Danlos syndrome (EDS). CHST14 encodes dermatan 4-O-sulfotransferase 1 (D4ST1), which transfers active sulfate to dermatan. In the mutants observed in the patients, its enzyme activity was almost completely lost and dermatan sulfate of decorin proteoglycan, a key regulator of collagen fibril assembly, was completely lost and replaced by chondroitin sulfate (CS) in the patients' fibroblasts. This may suggest that the replacement to inflexible CS, which intolerant to the mechanical compression, resulted in the impaired collagen bundle formation.

Research Products

• [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, Sugahara K, Matsumoto N.
  • Journal Title: Human Mutation (8) Pages: 966-974
  • Peer Reviewed
• [Journal Article] A New Ehlers-Danlos Syndrome With Craniofacial Characteristics, Congenital Multiple Contractures, and Progressive Joint and Skin Laxity and Multisystem Fragility related Manifestations. (2010)
  • Author(s): Kosho T, Miyake N, Hatamochi A, Takahashi J, Kato H, Miyahara T, Igawa Y, Yasui H, Ishida T, Ono K, Kosuda T, Inoue A, Kohyama M, Hattori T, Ohashi H, Nishimura G, Kawamura R, Wakui K, Fukushima Y, Matsumoto N.
  • Journal Title: American Journal of Medical Genetics A (152) Pages: 1333-1346
  • 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.
  • 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: American Journal of Medical Genetics A (in press)
  • Peer Reviewed
• [Presentation] Loss-of-function mutations of CHST14 cause a new type of autosomal recessive Ehlers-Danlos syndrome. (2010)
  • Author(s): Miyake N, Kosho T, Mizumoto S, Furuichi T, Hatamochi A, Ikegawa S, Yamada S, Sugahara K, Matsumoto N.
  • Organizer: American Society of Human Genetics (oral presentation)
  • Place of Presentation: アメリカ・ワシントンDC
  • Year and Date: 2010-11-03
• [Presentation] Carbohydrate sulfotrans-ferase 14 abnormality in human. (2010)
  • Author(s): Miyake N.
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 埼玉県大宮市(招待講演)
  • Year and Date: 2010-10-28
• [Patent(Industrial Property Rights)] エーラス・ダンロス症候群患者又は保因者の検出方法 (2009)
  • Inventor(s): 松本直通、三宅紀子
  • Industrial Property Rights Holder: 公立大学法人 横浜市立大学
  • Industrial Property Number: 特許,特願2009-219304 (P200-219304)
  • Filing Date: 2009-09-24