Molecular genetic study for retinitis pigmentosa

• Project/Area Number: 25462738
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Hayashi Takaaki 東京慈恵会医科大学, 医学部, 准教授 (10297418)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 網膜色素変性 / レーベル先天黒内障 / 分子遺伝学的 / 次世代シークエンサ / 全エクソーム解析 / 遺伝子変異 / 脳回状脈絡膜萎縮 / CNGA1変異 / RPE65変異 / 分子遺伝学 / 遺伝子 / 変異 / 遺伝性疾患 / 家族歴 / 先天盲 / 錐体杆体ジストロフィ / ヒトゲノム / 遺伝子解析 / エクソーム解析 / 臨床遺伝学 / Leber先天盲

Outline of Final Research Achievements

Retinitis pigmentosa is the most common inherited retinal dystrophy. Molecular genetic mechanisms of retinitis pigmentosa have not been fully elucidated so far because of a variety of causative genes and their mutations. In this study, we performed molecular genetic analysis to find out causative gene mutations and identified some of new gene mutations, which were different from the mutations reported in Europe and USA. We confirm that our results enable us to perform precise diagnostic approach and genetic counseling, and could be beneficial for promising next-generation treatments such as gene replacement and regenerative medicine therapies.

Research Products

• [Journal Article] Closure of a full-thickness macular hole without vitrectomy in choroideremia (2017)
  • Author(s): Ishikawa K, Gekka T, Hayashi T, Kikuchi S, Kameya S, Tsuneoka H
  • Journal Title: Clin Exp Optom Volume: 100 Issue: 3 Pages: 294-295
  • DOI: 10.1111/cxo.12467
  • Peer Reviewed
• [Journal Article] In vivo imaging of a cone mosaic in a patient with achromatopsia associated with a GNAT2 variant. (2017)
  • Author(s): Ueno S, Nakanishi A, Kominami T, Ito Y, Hayashi T, Yoshitake K, Kawamura Y, Tsunoda K, Iwata T, Terasaki H.
  • Journal Title: Jpn J Ophthalmol Volume: 61 Issue: 1 Pages: 92-98
  • DOI: 10.1007/s10384-016-0484-7
  • NAID: 210000179265
  • Peer Reviewed / Open Access
• [Journal Article] Differences in ocular findings in two siblings: one with complete and other with incomplete achromatopsia (2017)
  • Author(s): Ueno S, Nakanishi A, Sayo A, Kominami T, Ito Y, Hayashi T, Tsunoda K, Iwata T, Terasaki H
  • Journal Title: Doc Ophthalmol Volume: 134 Issue: 2 Pages: 141-147
  • DOI: 10.1007/s10633-017-9577-y
  • Peer Reviewed / Open Access
• [Journal Article] Foveal Hypoplasia in Patients with Stickler Syndrome (2017)
  • Author(s): Matsushita I, Nagata T, Hayashi T, Kimoto K, Kubota T, Ohji M, Kusaka S, Kondo H.
  • Journal Title: Ophthalmology Volume: in press Issue: 6 Pages: 896-902
  • DOI: 10.1016/j.ophtha.2017.01.046
  • Peer Reviewed
• [Journal Article] RPE65 mutations in two Japanese families with Leber congenital amaurosis. (2016)
  • Author(s): Katagiri S, Hayashi T, Yoshitake K, Akahori M, Ikeo K, Gekka T, Tsuneoka H, Iwata T
  • Journal Title: Ophthalmic Genetics Volume: 37 Issue: 2 Pages: 161-169
  • DOI: 10.3109/13816810.2014.991931
  • Peer Reviewed
• [Journal Article] Clinical and genetic findings of autosomal recessive bestrophinopathy in Japanese cohort. (2016)
  • Author(s): Nakanishi A, Ueno S, Hayashi T, Katagiri S, Kominami T, Ito Y, Gekka T, Masuda Y, Tsuneoka H, Shinoda K, Hirakata A, Inoue M, Fujinami K, Tsunoda K, Iwata T, Terasaki H.
  • Journal Title: Am J Ophthalmol. Volume: 168 Pages: 86-94
  • DOI: 10.1016/j.ajo.2016.04.023
  • NAID: 120005868242
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epidemiology of retinal detachment in patients with Stickler syndrome associated with COL2A1 gene mutations (2016)
  • Author(s): Kondo H, Matsushita I, Nagata T, Hayashi T, Kakinoki M, Uchino E, Kondo M, Ohji M, Kusaka S
  • Journal Title: Hum Genome Var Volume: 3 Issue: 1 Pages: 16018-16018
  • DOI: 10.1038/hgv.2016.18
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel heterozygous splice site OPA1 mutation causes exon 10 skipping in Japanese patients with dominant optic atrophy (2016)
  • Author(s): Iida K, Ohkuma Y, Hayashi T, Katagiri S, Fujita T, Tsunoda K，Yamada H, Tsuneoka H
  • Journal Title: Ophthalmic Genet Volume: 37 Issue: 3 Pages: 354-356
  • DOI: 10.3109/13816810.2015.1066829
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel RP1L1 variants and genotype-photoreceptor microstructural phenotype associations in cohort of Japanese patients with occult macular dystrophy. (2016)
  • Author(s): Fujinami K, Kameya S, Kikuchi S, Ueno S, Kondo M, Hayashi T, Shinoda K, Machida S, Kuniyoshi K, Kawamura Y, Akahori M, Yoshitake K, Katagiri S, Nakanishi A, Sakuramoto H, Ozawa Y, Tsubota K, Yamaki K, Mizota A, Terasaki H, Miyake Y, Iwata T, Tsunoda K.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 57 Issue: 11 Pages: 4837-4846
  • DOI: 10.1167/iovs.16-19670
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New truncation mutation of the NR2E3 gene in a Japanese patient with enhanced S-cone syndrome. (2016)
  • Author(s): Kuniyoshi K, Hayashi T, Sakuramoto H, Mishima H, Tsuneoka H, Tsunoda K, Iwata T, Shimomura Y.
  • Journal Title: Jpn J Ophthalmol Volume: 60 Issue: 6 Pages: 476-485
  • DOI: 10.1007/s10384-016-0470-0
  • Peer Reviewed
• [Journal Article] Spontaneous resolution of large macular retinoschisis in enhanced S-cone syndrome (2016)
  • Author(s): Hayashi T, Gekka T, Tsuneoka H
  • Journal Title: Ophthalmic Surg Lasers Imaging Retina Volume: 47 Issue: 2 Pages: 187-190
  • DOI: 10.3928/23258160-20160126-15
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High resolution adaptive optics retinal image analysis at early-stage central areolar choroidal dystrophy with PRPH2 mutation (2016)
  • Author(s): Gocho K, Akeo K, Itoh N, Kameya S, Hayashi T, Katagiri S, Gekka T, Ohkuma Y, Tsuneoka H, Takahashi H.
  • Journal Title: Ophthalmic Surg Lasers Imaging Retina Volume: 47 Issue: 12 Pages: 1115-1126
  • DOI: 10.3928/23258160-20161130-05
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Somatic instability of expanded CAG repeats of ATXN7 in Japanese patients with spinocerebellar ataxia type 7 (2015)
  • Author(s): Katagiri S，Hayash T，Takeuchi T，Yamada H，Gekka T，Kawabe K，et al.
  • Journal Title: Doc Ophthalmol Volume: 130 Issue: 3 Pages: 189-195
  • DOI: 10.1007/s10633-015-9488-8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Multimodal imaging of a case of peripheral cone dystrophy (2015)
  • Author(s): Ito N，Kameya S，Gocho K，Hayashi T，Kikuchi S，Katagiri S，et al.
  • Journal Title: Doc Ophthalmol Volume: 130 Issue: 3 Pages: 241-251
  • DOI: 10.1007/s10633-015-9490-1
  • Peer Reviewed
• [Journal Article] Mutation analysis of BEST1 in Japanese patients with Best’s vitelliform macular dystrophy (2015)
  • Author(s): Katagiri S，Hayashi T，Ohkuma Y，Sekiryu T，Takeuchi T，Gekka T，et al.
  • Journal Title: Br J Ophthalmol Volume: 99 Issue: 11 Pages: 1577-1582
  • DOI: 10.1136/bjophthalmol-2015-306830
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel C8orf37 mutations in patients with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia (2015)
  • Author(s): Katagiri S, Hayashi T, Yoshitake K, Akahori M, Ikeo K, Gekka T, Tsuneoka H, Iwata T
  • Journal Title: Ophthalmic Genet Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] RPE65 mutations in two Japanese families with Leber congenital amaurosis (2015)
  • Author(s): Katagiri S, Hayashi T, Kondo M, Tsukitome H, Yoshitake K, Akahori M, Ikeo K, Tsuneoka H, Iwata T
  • Journal Title: Ophthalmic Genet Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel C8orf37 Mutations in Patients with Early-onset Retinal Dystrophy, Macular Atrophy, Cataracts, and High Myopia. (2014)
  • Author(s): Katagiri S, Hayashi T, Yoshitake K, Akahori M, Ikeo K, Gekka T, Tsuneoka H, Iwata T.
  • Journal Title: Ophthalmic Genetics Volume: 12 Pages: 1-8
  • DOI: 10.3109/13816810.2014.949380
  • Peer Reviewed
• [Journal Article] OAT mutations and clinical features in two Japanese brothers with gyrate atrophy of the choroid and retina (2014)
  • Author(s): Katagiri S, Gekka T, Hayashi T, Ida H, Ohashi T, Eto Y, Tsuneoka H
  • Journal Title: Doc Ophthalmol Volume: 128 Issue: 2 Pages: 137-148
  • DOI: 10.1007/s10633-014-9426-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Autosomal recessive cone-rod dystrophy associated with compound heterozygous mutations in the EYS gene. (2014)
  • Author(s): Katagiri S, Akahori M, Hayashi T, Yoshitake K, Gekka T, Ikeo K, Tsuneoka H, Iwata T.
  • Journal Title: Doc Ophthalmol. Volume: 128(3) Issue: 3 Pages: 211-217
  • DOI: 10.1007/s10633-014-9435-0
  • Peer Reviewed
• [Journal Article] RHO mutations (p.W126L and p.A346P) in two Japanese families with autosomal dominant retinitis pigmentosa (2014)
  • Author(s): Katagiri S, Hayashi T, Akahori M, Itabashi T, Nishio J, Yoshitake K, Furuno M, Ikeo K, Okada T, Tsuneoka H, Iwata T
  • Journal Title: J Ophthalmol Volume: 2014 Pages: 210947-210947
  • DOI: 10.1155/2014/210947
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] KRT12 mutations and in vivo confocal microscopy in two Japanese families with Meesmann corneal dystrophy (2014)
  • Author(s): Ogasawara M, Matsumoto Y, Hayashi T, Ohno K, Yamada H, Kawakita T, et al.
  • Journal Title: American Journal of Ophthalmology Volume: 157 Issue: 1 Pages: 93-102
  • DOI: 10.1016/j.ajo.2013.08.008
  • Peer Reviewed
• [Journal Article] Whole-exome sequencing identifies a novel ALMS1 mutation (Q2051X) in two Japanese bothers with Alstrom Syndrome (2013)
  • Author(s): Katagiri S, Yoshitake K, Akahori M, Hayashi T, Furuno M, Nishino J, Ikeo K, Tsuneoka H, Iwata T.
  • Journal Title: Molecular Vision Volume: 19 Pages: 2393-2406
  • Peer Reviewed
• [Presentation] OPA1遺伝子欠失を認めた常染色体優性視神経萎縮の家系 (2016)
  • Author(s): 林 孝彰
  • Organizer: 第70回 日本臨床眼科学会
  • Place of Presentation: 京都
  • Year and Date: 2016-11-03
• [Presentation] 家族歴聴取を契機に診断されたS錐体1色覚の1家系 (2016)
  • Author(s): 林 孝彰
  • Organizer: 第64回日本臨床視覚電気生理学会
  • Place of Presentation: 伊勢志摩
  • Year and Date: 2016-09-30
• [Presentation] シンポジウム「診断に苦慮した症例・珍しい症例」眼底に白点がみられた2例 (2016)
  • Author(s): 林 孝彰
  • Organizer: 第64回日本臨床視覚電気生理学会
  • Place of Presentation: 伊勢志摩
  • Year and Date: 2016-09-30
• [Presentation] サブスペシャリティサンデー「小児眼底疾患のアップデート」網膜変性・遺伝性疾患 (2016)
  • Author(s): 林 孝彰
  • Organizer: 120回日本眼科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-07
• [Presentation] シンポジウム「遺伝性網脈絡膜変性疾患の遺伝型と臨床型」遺伝性錐体機能不全の遺伝型と臨床型 (2016)
  • Author(s): 林 孝彰
  • Organizer: 120回日本眼科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-07
• [Presentation] 網膜色素変性の遺伝子異常と遺伝子解析について (2016)
  • Author(s): 林 孝彰
  • Organizer: 第11回JRPS網脈絡膜変性フォーラム
  • Place of Presentation: 伊勢
• [Presentation] コロイデレミアに合併した黄斑円孔が自然閉鎖を認めた1例 (2015)
  • Author(s): 石川邦裕、月花環、林孝彰、常岡寛
  • Organizer: 第54回日本網膜硝子体学会総会・第32回日本眼循環学会
  • Place of Presentation: 東京
  • Year and Date: 2015-12-04
• [Presentation] 網膜硝子体ジストロフィのトータルケア-集中講義版- (2015)
  • Author(s): 堀田喜裕、近藤寛之、近藤峰生、高橋政代、林孝彰
  • Organizer: 第69回 日本臨床眼科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-22
• [Presentation] Biallelic mutation of BEST1 causes ARB with varying degreees of severity in two Japanese families (2015)
  • Author(s): Nakaminishi A, Ueno S, Hayashi T, Katagiri S, Iwata T, Terasaki H.
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: Colorado, USA
  • Year and Date: 2015-05-03
• [Presentation] Autosomal Recessive Bestrophinopathyの2家系 (2015)
  • Author(s): 中西絢美、上野真治、林孝彰、片桐聡、岩田岳、寺崎浩子
  • Organizer: 第119回日本眼科学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2015-04-16
• [Presentation] 網膜色素変性とその類縁疾患に対する遺伝子診断の最前線 (2014)
  • Author(s): 林 孝彰
  • Organizer: 第62回日本臨床視覚電気生理学会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-03 – 2014-10-04
  • Invited
• [Presentation] Whole exome analysis identifies frequent cnga1 mutations in japanese population with autosomal recessive retinitis pigmentosa (2014)
  • Author(s): Katagiri S, Akahori M, Sergeev Y, Yoshitake K, Kazuho Ikeo K, Furuno M, Hayashi T, Mineo Kondo M, Ueno S, Tsunoda K, Shinoda K, Kuniyoshi K, Tsurusaki Y, Matsumoto N, Sasano H, Ohkuma Y, Tsuneoka H, Iwata T
  • Organizer: XXI Biennial Meeting of the International Society for Eye Research (ISER)
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2014-07-20 – 2014-07-24
• [Presentation] BEST1 mutations in Japanese patients with Best vitelliform macular dystrophy (2014)
  • Author(s): Katagiri S, Hayashi T, Sekiryu T, Gekka T, Akahori M, Sasano H, Ohkuma Y, Iwata T, Tsuneoka H
  • Organizer: The Association for Research in Vision and Ophthalmology
  • Place of Presentation: フロリダ
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] A novel ALMS1 mutation (p.Q2051X) with Alström syndrome in one consanguineous Japanese family (2014)
  • Author(s): Katagiri S, Hayashi T, Akahori, Iwata T, Tsuneoka H
  • Organizer: World Ophthalmology Congress 2014
  • Place of Presentation: 東京
  • Year and Date: 2014-04-02 – 2014-04-06
• [Presentation] Adaptive optics fundus camera reveals parafoveal cone loss in peripheral cone dystrophy (2014)
  • Author(s): Itoh N, Hayashi T, Gocho K, Kameya S, Tsuneoka H.
  • Organizer: World Ophthalmology Congress 2014
  • Place of Presentation: 東京
  • Year and Date: 2014-04-02 – 2014-04-06