顔面と陰部に色素斑が多発する遺伝性全身性メラニン色素異常症（仮称）の原因解明

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26670526
• Research Institution: Nagoya University
• Principal Investigator: 杉浦 一充 名古屋大学, 医学(系)研究科(研究院), 准教授 (70335032)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 遺伝性全身性メラニン色素異常症 / 遺伝性皮膚疾患 / c-kit

Outline of Annual Research Achievements

1.遺伝性全身性メラニン色素異常症原因遺伝子を同定した。 6 人の患者を含む家族12 人から末梢血を採取し、白血球のDNA を抽出した。患者3 人と患者家族の健常人1 人の全エクソームシーケンス法で解析し、候補原因遺伝子を絞り込んだ。全エクソームシーケンス法を行わなかった家族のDNA を用いて変異解析、ハプロタイプ解析などを実施して原因遺伝子UIMSH3(仮称）を同定した。。2.UIMSH3 のメラニン合成への関与とその役割:無色素性のメラノーマ由来細胞株A375 とSK-MEL28 に野生型UIMSH3 あるいは本家系で発見された病的変異型UIMSH3 を遺伝子導入し、恒常的に発現する細胞株を作成した。メラニンの合成、c-kit kinase の活性化について検討した。

Research Products

• [Journal Article] Unilateral generalized linear porokeratosis with nail dystrophy. (2016)
  • Author(s): Kono M, Yokoyama N, Ogawa Y, Takama H, Sugiura K, Akiyama M.
  • Journal Title: J Dermatol Volume: 43 Pages: 286-7.
  • DOI: 10.1111/1346-8138.13204.
  • Peer Reviewed
• [Journal Article] Noteworthy clinical findings of harlequin ichthyosis: Digital autoamputation caused by cutaneous constriction bands in a case with novel ABCA12 mutations. (2016)
  • Author(s): Tanahashi K, Sugiura K, Sato T, Akiyama M.
  • Journal Title: Br J Dermatol Volume: 174 Pages: 689-91.
  • DOI: 10.1111/bjd.14228.
  • Peer Reviewed
• [Journal Article] Bi-allelic nonsense mutations in ABHD5 underlie a mild phenotype of Dorfman-Chanarin syndrome. (2016)
  • Author(s): Takeichi T, Sugiura K, Tso S, Simpson MA, McGrath JA, Akiyama M.
  • Journal Title: J Dermatol Sci Volume: 81 Pages: 134-6.
  • DOI: 10.1016/j.jdermsci.2015.10.015.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Anti-transcription intermediary factor 1-γ antibody-positive clinically amyopathic dermatomyositis complicated by interstitial lung disease and breast cancer. (2016)
  • Author(s): Ogawa M, Sugiura K, Yokota K, Muro Y, Akiyama M.
  • Journal Title: J Eur Acad Dermatol Venereol Volume: 30 Pages: 373-5.
  • DOI: 10.1111/jdv.12797.
  • Peer Reviewed
• [Journal Article] Serum thymus and activation-regulated chemokine (TARC/CCL17) levels reflect the disease activity in a patient with bullous pemphigoid. (2016)
  • Author(s): Nin-Asai R, Muro Y, Sekiya A, Sugiura K, Akiyama M.
  • Journal Title: J Eur Acad Dermatol Venereol Volume: 30 Pages: 327-8.
  • DOI: 10.1111/jdv.12719.
  • Peer Reviewed
• [Journal Article] Apparent homozygosity due to compound heterozygosity of one point mutation and an overlapping exon deletion mutation in ABCA12. (2015)
  • Author(s): Shibata A, Sugiura K, Suzuki A, Ichiki T, Akiyama M.
  • Journal Title: J Dermatol Sci Volume: 80 Pages: 196-202.
  • DOI: 10.1016/j.jdermsci.2015.10.003.
  • Peer Reviewed
• [Journal Article] Magnetic resonance imaging findings are useful for evaluating the three dimensional development and follow-up of linear lupus erythematosus profundus. (2015)
  • Author(s): Ogawa M, Muro Y, Sugiura K, Sakakibara A, Akiyama M.
  • Journal Title: Lupus Volume: 24 Pages: 1214-6.
  • DOI: 10.1177/0961203315574559.
  • Peer Reviewed
• [Journal Article] What are the "True" Pathogenic Anti-desmoglein Antibodies? (2015)
  • Author(s): Muro Y, Sugiura K, Akiyama M.
  • Journal Title: Acta Derm Venereol Volume: 95 Pages: 872-4.
  • DOI: 10.2340/00015555-2119.
  • Peer Reviewed / Open Access
• [Journal Article] Successful treatment with infliximab of sibling cases with generalized pustular psoriasis caused by deficiency of interleukin-36 receptor antagonist. (2015)
  • Author(s): Sugiura K, Endo K, Akasaka T, Akiyama M.
  • Journal Title: J Eur Acad Dermatol Venereol Volume: 29 Pages: 2054-6.
  • DOI: 10.1111/jdv.12590.
  • Peer Reviewed
• [Journal Article] Lamellar ichthyosis caused by a previously unreported homozygous ALOXE3 mutation in East Asia. (2015)
  • Author(s): Sugiura K, Akiyama M.
  • Journal Title: Acta Derm Venereol Volume: 95 Pages: 858-9.
  • DOI: 10.2340/00015555-2022.
  • Peer Reviewed / Open Access
• [Journal Article] Porokeratotic eccrine ostial and dermal duct nevus with a somatic homozygous or monoallelic variant of connexin 26. (2015)
  • Author(s): Noda K, Sugiura K, Kono M, Akiyama M.
  • Journal Title: J Dermatol Sci Volume: 80 Pages: 74-6.
  • DOI: 10.1016/j.jdermsci.2015.07.003.
  • Peer Reviewed
• [Journal Article] Novel indel mutation of STS underlies a new phenotype of self-healing recessive X-linked ichthyosis. (2015)
  • Author(s): Takeichi T, Sugiura K, Chao-Kai Hsu CK, Tanahashi K, Takama H, Michael A Simpson, MA, McGrath JA, Akiyama M.
  • Journal Title: J Dermatol Sci Volume: 79 Pages: 317-9.
  • DOI: 10.1016/j.jdermsci.2015.07.001.
  • Peer Reviewed
• [Journal Article] High incidence of cancer in anti-small ubiquitin-like modifier activating enzyme antibody-positive dermatomyositis. (2015)
  • Author(s): Muro Y, Sugiura K, Nara M, Sakamoto I, Suzuki N, Akiyama M.
  • Journal Title: Rheumatology (Oxford) Volume: 54 Pages: 1745-7.
  • DOI: 10.1093/rheumatology/kev247.
  • Peer Reviewed
• [Journal Article] Topical minoxidil improves congenital hypotrichosis caused by LIPH mutations. (2015)
  • Author(s): Tanahashi K, Sugiura K, Akiyama M.
  • Journal Title: Br J Dermatol Volume: 173 Pages: 865-6.
  • DOI: 10.1111/bjd.13790.
  • Peer Reviewed
• [Journal Article] Impetigo herpetiformis with IL36RN mutations in a Chinese patient: A founder haplotype of c.115+6T>C in East Asia. (2015)
  • Author(s): Sugiura K, Nakasuka A, Kono H, Kono M, Akiyama M.
  • Journal Title: J Dermatol Sci Volume: 79 Pages: 319-20.
  • DOI: 10.1016/j.jdermsci.2015.06.003.
  • Peer Reviewed
• [Journal Article] Dowling-Degos disease with mutations in POFUT1 is clinicopathologically distinct from reticulate acropigmentation of Kitamura. (2015)
  • Author(s): Kono M, Suganuma M, Takama H, Zarzoso I, Saritha M, Bodet D, Aboobacker S, Kaliaperumal K, Suzuki T, Tomita Y, Sugiura K, Akiyama M.
  • Journal Title: Br J Dermatol Volume: 173 Pages: 584-6.
  • DOI: 10.1111/bjd.13702.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A case of annular pustular psoriasis with heterozygous IL36RN mutation. (2015)
  • Author(s): Miyake T, Umemura H, Doi Y, Kousogabe J, Tsuji K, Hamada T, Sugiura K, Aoyama Y, Akiyama M, Iwatsuki K.
  • Journal Title: Eur J Dermatol Volume: 25 Pages: 349-50.
  • Peer Reviewed
• [Journal Article] The novel GJB3 mutation p.Thr202Asn in the M4 transmembrane domain underlies erythrokeratodermia variabilis. (2015)
  • Author(s): Sugiura K, Arima M, Matsunaga K, Akiyama M.
  • Journal Title: Br J Dermatol Volume: 173 Pages: 349-50.
  • DOI: 10.1111/bjd.13641.
  • Peer Reviewed
• [Journal Article] Elderly-onset generalized pustular psoriasis without previous history of psoriasis vulgaris. (2015)
  • Author(s): Aizu T, Matsui A, Takiyoshi N, Akasaka E, Kaneko T, Nakano H, Sugiura K, Akiyama M, Sawamura D.
  • Journal Title: Case Rep Dermatol Volume: 7 Pages: 187-93.
  • DOI: 10.1159/000438505.
  • Peer Reviewed / Open Access
• [Journal Article] Update on autosomal recessive congenital ichthyosis: mRNA analysis using hair samples is a powerful tool for genetic diagnosis. (2015)
  • Author(s): Sugiura K, Akiyama M.
  • Journal Title: J Dermatol Sci Volume: 79 Pages: 4-9.
  • DOI: 10.1016/j.jdermsci.2015.04.009.
  • Peer Reviewed
• [Journal Article] Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation. (2015)
  • Author(s): Ohno Y, Nakamichi S, Ohkuni A, Kamiyama N, Naoe A, Tsujimura H, Yokose U, Sugiura K, Ishikawa J, Akiyama M, Kihara A.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 112 Pages: 7707-12.
  • DOI: 10.1073/pnas.1503491112.
  • Peer Reviewed
• [Journal Article] Annular elastolytic giant cell granuloma successfully treated with minocycline hydrochloride. (2015)
  • Author(s): Nanbu Ai, Sugiura K, Kono M, Muro Y, Akiyama M.
  • Journal Title: Acta Derm Venereol Volume: 95 Pages: 756-7.
  • DOI: 10.2340/00015555-2056.
  • Peer Reviewed / Open Access
• [Journal Article] Pustular psoriasis like lesions associated with hereditary lactate dehydrogenase M-subunit deficiency without interleukin-36 receptor antagonist mutation: Long-term follow-ups of two cases. (2015)
  • Author(s): Ito T, Aoshima M, Sugiura K, Fujiyama N, Ito N, Sakabe JI, Akiyama M, Maekawa M, Tokura Y.
  • Journal Title: Br J Dermatol Volume: 172 Pages: 1674-6.
  • DOI: 10.1111/bjd.13590.
  • Peer Reviewed
• [Journal Article] Diversity of humoral responses to thecentromere proteins among HCV-relatedchronic liver disease, PBC and AIH patients. (2015)
  • Author(s): Himoto T, Tanaka N, Saito A, Muro Y, Sugiura K, Tani J, Miyoshi H, Morishita A, Yoneyama H, Haba R, Masaki T.
  • Journal Title: Clin Res Hepatol Gastroenterol Volume: 39 Pages: 222-9.
  • DOI: 10.1016/j.clinre.2014.08.004.
  • Peer Reviewed
• [Journal Article] TRPS1 haploinsufficiency results in increased STAT3 and SOX9 mRNA expression in hair follicles in trichorhinophalangeal syndrome. (2015)
  • Author(s): Shibata A, Tanahashi K, Sugiura K, Akiyama M.
  • Journal Title: TRPS1 haploinsufficiency results in increased STAT3 and SOX9 mRNA expression in hair follicles in trichorhinophalangeal syndrome. Volume: 95 Pages: 620-1.
  • DOI: 10.2340/00015555-1948.
  • Peer Reviewed / Open Access
• [Presentation] 皮膚科の自己炎症性疾患、DITRAとCAMPS：遺伝学的研究からわかってきたこと (2016)
  • Author(s): 杉浦一充
  • Organizer: 第40回皮膚科免疫セミナー
  • Place of Presentation: 経団連会館 東京都千代田区
  • Year and Date: 2016-03-05
  • Invited
• [Presentation] Genetic background of pustular psoriasis (2015)
  • Author(s): Sugiura K.
  • Organizer: 日本研究皮膚科学会第40回年次学術大会・総会
  • Place of Presentation: 岡山コンベンションセンター 岡山県岡山市
  • Year and Date: 2015-12-13
  • Invited
• [Presentation] 膿疱症 up-to-date (2015)
  • Author(s): 杉浦一充
  • Organizer: 平成27年度生涯教育講演会第274回 日本皮膚科学会東海地方会
  • Place of Presentation: 大正製薬名古屋支店 愛知県名古屋市
  • Year and Date: 2015-12-06
  • Invited
• [Presentation] 先天性縮毛症・乏毛症 (2015)
  • Author(s): 杉浦一充
  • Organizer: 第20回日本臨床毛髪学会学術集会
  • Place of Presentation: 総合あいしんセンター 高知県高知市
  • Year and Date: 2015-12-05
  • Invited
• [Presentation] 膿疱症 (2015)
  • Author(s): 杉浦一充
  • Organizer: 平成27年度日本皮膚科学会研修講習会（必須Aコース）
  • Place of Presentation: 学術総合センター 東京都千代田区
  • Year and Date: 2015-08-29
  • Invited
• [Presentation] 膿疱性乾癬とAGEPの関係 (2015)
  • Author(s): 杉浦一充
  • Organizer: 第114回日本皮膚科学会総会
  • Place of Presentation: パシフィコ横浜 神奈川県横浜市
  • Year and Date: 2015-05-30
  • Invited
• [Patent(Industrial Property Rights)] 関節症性乾癬モデル動物及び膿疱性乾癬モデル動物 (2015)
  • Inventor(s): 秋山真志、杉浦一充、柴田章貴
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2015-181223
  • Filing Date: 2015-09-14
• [Patent(Industrial Property Rights)] インターロイキン３６受容体アンタゴニスト欠損症の治療薬 (2015)
  • Inventor(s): 秋山真志、杉浦一充、柴田章貴
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2015-254560
  • Filing Date: 2015-12-25