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厚生労働科学研究費補助金（難治性疾患等政策研究事業）
分担研究報告書
「先天性および若年性の視覚聴覚二重障害に対する一体的診療体制に関する研究」
研究分担者 藤波 芳
国立病院機構東京医療センター・臨床研究センター、視覚研究部・視覚生理学研究室・室長
研究要旨
視機能評価法構築、聴覚・視覚障害に関する臨床的評価、分子遺伝学的評価、データベース構 築ならびに、「先天性および若年性の視覚聴覚二重障害の原因となる難病の診療マニュアル」の うち、ゴールデンハー症候群、神経線維腫症、トリーチャー・コリンズ症候群の執筆を行った。
Ａ．研究目的
視覚聴覚二重障害診療における臨床的評価、分 子遺伝学的評価、データベース構築、並びに診 療マニュアル作成に従事し、診療科横断型診療 体制構築に寄与する。
Ｂ．研究方法
１、東京医療センター視覚聴覚二重障害症例検 討会において、臨床検査所見、分子遺伝学的所 見について、精査・討議を行い、それぞれにつ いての評価を行う。
２、視覚聴覚二重障害症例の集積を目的とした データベースにおける、眼科臨床検査に対する 登録項目の作成ならびに精査を通して、データ ベース構築を行う。
３、「先天性および若年性の視覚聴覚二重障害 の原因となる難病の診療マニュアル」ゴールデ ンハー症候群、神経線維腫症、トリーチャー・
コリンズ症候群の執筆を行う為、文献・ガイド ライン・各種学会の診断基準・治療指針の調査 を行う。
(倫理面への配慮) 該当なし
Ｃ．研究結果
１、全5回の視覚聴覚二重障害症例検討会におい て10症例の確定診断ならびに治療方針が決定さ れた。
２、データベースにおける、眼科臨床検査の登 録項目とその選択内容が決定された。
３、「先天性および若年性の視覚聴覚二重障害 の原因となる難病の診療マニュアル」のうち、
ゴールデンハー症候群、神経線維腫症、トリー チャー・コリンズ症候群の執筆を行った。
Ｄ．考察
視覚聴覚二重障害診療における臨床的評価、分 子遺伝学的評価、データベース構築、診療マニ ュアルの作成は研究の実効性を高めるものであ った。これらの研究活動については、持続性が 社会実装の鍵となる為、継続的な活動が必要と なる。
Ｅ．結論
「先天性および若年性の視覚聴覚二重障害」の 臨床的評価、分子遺伝学的評価、データベース 構築、ならびにマニュアル作成を通して、実行 性の高い診療科横断的診療体制の構築が望まれ る。
Ｆ．研究発表 1. 論文発表
(*First Author, †corresponding author)
Fujinami K*
†. Yang L*, Joo K* et al. Clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake Disease): East Asia Occult Macular Dystrophy Studies Report Number 1. Ophthalmology. 2019 Oct;126(10):1432‑1444.
25 Yang L*, Fujinami K*
†,…, Fujinami‑Yokokawa Y et al. Genetic Spectrum of EYS‑associated Retinal Disease in a Large Japanese Cohort:
Identification of Disease‑associated Variants with Relatively High Allele Frequency. Sci Rep.
2020 Mar 26;10(1):5497.
Liu X*, Fujinami K*
†.…, Fujinami‑Yokokawa Y et al. Clinical and genetic characteristics of 15 affected patients from 12 Japanese families with GUCY2D‑associated retinal disorder.
Transl Vis Sci Technol. In press.
Kameya S*, Fujinami K,*, Ueno S et al.
Phenotypical Characteristics of
POC1B‑Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal
Funduscopic Appearance. Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3432‑3446.
Fujinami‑Yokokawa Y*, Pontikos N*, Yang L, ,…, Fujinami K
†, et al. Prediction of Causative Genes in Inherited Retinal Disorders from Spectral‑Domain Optical Coherence Tomography Utilizing Deep Learning Techniques. J Ophthalmol. 2019 Apr 9;2019:1691064.
Khan, M., Cornelis, S. S., del Pozo‑Valero, M,…, Fujinami K, et al. Resolving the dark matter of ABCA4 for 1,054 Stargardt disease probands through integrated genomics and
transcriptomics. Genet. Med. In press.
Katagiri S, Hayashi T, Nakamura M,…, Fujinami K, et al. RDH5‑related fundus albipunctatus in a large Japanese cohort. Invest Ophthalmol Vis Sci. In press.
Berry V, Georgiou1 M, Fujinami K et al.
Inherited Cataracts: Molecular Genetics, Clinical Features, Disease Mechanisms, and Novel Therapeutic Approaches. Br J Ophthalmol in press
Pontikos N,…, Fujinami K, Fujinami‑Yokokawa Y et al. Phenogenon: Gene to Phenotype
Associations for Rare Genetic Diseases. PLoS One. In press
Kuniyoshi K, Hayashi T, Kameya S,…, Fujinami K, et al. Clinical Course and Electron Microscopic Findings in Lymphocytes of Patients with DRAM2‑Associated Retinopathy. Int J Mol Sci. 2020 Feb 16;21(4).
Bouzia Z, Georgiou M, Hull S,…, Fujinami K, et al. GUCY2D‑Associated Leber Congenital Amaurosis: A Retrospective Natural History Study in Preparation for Trials of Novel Therapies. Am J Ophthalmol. 2020 Feb;210:59‑70.
Nakanishi A, Ueno S, Hayashi T,…, Fujinami K, et al. CHANGES OF CONE PHOTORECEPTOR MOSAIC IN AUTOSOMAL RECESSIVE BESTROPHINOPATHY. Retina.
2020 Jan;40(1):181‑186.
Georgiou M, Kane T, Tanna P,…, Fujinami K, et al. Prospective Cohort Study of Childhood‑Onset Stargardt Disease: Fundus Autofluorescence Imaging, Progression, Comparison with
Adult‑Onset Disease, and Disease Symmetry. Am J Ophthalmol. 2020 Mar;211:159‑175.
Mizobuchi K, Hayashi T, Katagiri S,…, Fujinami K, et al. Characterization of GUCA1A‑associated dominant cone/cone‑rod dystrophy: low
prevalence among Japanese patients with inherited retinal dystrophies. Sci Rep. 2019 Nov 14;9(1):16851.
Nakamura N, Tsunoda K, Mizuno Y,…, Fujinami K, et al. Clinical Stages of Occult Macular Dystrophy Based on Optical Coherence
Tomographic Findings. Invest Ophthalmol Vis Sci.
2019 Nov 1;60(14):4691‑4700.
Maeda‑Katahira A, Nakamura N, Hayashi T,…, Fujinami K, et al. Autosomal dominant optic atrophy with OPA1 gene mutations accompanied by auditory neuropathy and other systemic complications in a Japanese cohort. Mol Vis.
2019 Oct 5;25:559‑573.
Mawatari G, Fujinami K. Liu X, et al. Clinical and genetic characteristics of 14 patients from 13 Japanese families with RPGR‑associated retinal disorder: report of eight novel variants. Hum Genome Var. 2020 Feb 10;7:3.
Tsunoda K, Fujinami K. Yoshitake K, et al.
Late‑onset night blindness with peripheral flecks accompanied by progressive trickle‑like macular degeneration. Doc Ophthalmol. 2019 Dec;139(3):171‑184.
2. 学会発表
The Association for Research in Vision and
Ophthalmology (ARVO) 2019 Conference. 28
April‑2 May, 2019. Vancouver B.C., Canada.
26 E‑abstract
Fujinami K, et al. Japan Eye Genetics
Consortium: National Cohort Survey and Whole Exome Sequencing Results.
Fujinami‑Yokokawa Y, …, Fujinami K. Prediction of Causative Genes in Inherited Retinal Disorders from Spectral‑Domain Optical Coherence Tomography Utilizing Deep Learning Techniques.
Akiyama K, …, Fujinami K, et al. Internal limiting membrane peeling to prevent epiretinal membrane growth after retinal detachment repair: retinal surface wrinkling as a sign of proliferation.
The 57th Annual Symposium of the International Society for Clinical Electrophysiology of Vision (ISCEV). 7‑10 October, 2019. Seoul, Korea.
E‑abstract
Fujinami K, et al. Electrically Evoked Potentials Elicited by Transcorneal Electrical Stimulation in Healthy Human Subjects;
Detection of Peaks, Reaction to Increased Stimuli and Difference in State of Adaptation.
Liu X, …, Fujinami K. Clinical and Genetic Characteristics of East Asian Patients with Stargardt disease; EAStar Report No.1.
Joo K, …, Fujinami K, Woo SJ; on behalf of East Asia Inherited Retinal Disease Society.
Multimodal imaging of East Asian Patients with Occult Macular Dystrophy (Miyake s disease):
EAOMD Report No. 3.
Fujinami‑Yokokawa Y, Fujinami K, et al.
Electrically Evoked Potentials Elicited by Transcorneal Electrical Stimulation in Healthy Human Subjects; Comparison with Pattern Visual Evoked Potentials, Pattern Electroretinograms, and Photopic Negative Responses.
Suzuki Y, …, Fujinami K. Full‑Field Pupillary Light Responses and Full‑Field Scotopic Thresholds (FST) for Colour Stimuli in Healthy Human Subjects.
Akiyama K, Fujinami K, et al. Retinal
dysfunction at the macula in patients with a
macula‑on rhegmatogenous retinal
detachment: evaluation of the photopic negative response.
The 1st Symposium of East Asia Inherited Retinal Disease Society (EAIRDs). 11 October, 2019.
Seoul, Korea.
E‑abstract
Fujinami K, et al. Clinical and Genetic Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake s disease);
EAOMD Report No.1.
Yang L, …, Fujinami K; on behalf of East Asia Inherited Retinal Disease Society. Functional Characteristics of East Asian Patients with Occult Macular Dystrophy (Miyake s disease);
EAOMD Report No.2
Yang L, …, Fujinami K; on behalf of East Asia Inherited Retinal Disease Society. Spectrum of Occult Macular Dystrophy: Investigation of RP1L1 Positive and RP1L1 Negative OMD; EAOMD Report No.5.
Fujinami‑Yokokawa Y, …, Fujinami K; on behalf of East Asia Inherited Retinal Disease Society.
Genotype Phenotype Association in East Asian Patients with Occult Macular Dystrophy (Miyake s disease); EAOMD Report No.4.
Fujinami‑Yokokawa Y, …, Fujinami K; on behalf of East Asia Inherited Retinal Disease Society.
Investigation of the origin of p.R45W causative for Occult Macular Dystrophy (Miyake s disease) in the East Asian population; EAOMD Report No.6.
Liu X, …, Fujinami K, Yin Z, Li S; on behalf of East Asia Inherited Retinal Disease Society.
Clinical and Genetic Investigation of Stargardt disease in a Chinese Cohort; EAStar China Report 1.
Ｇ．知的財産権の出願・登録状況（予定を含む。） 1. 特許取得
該当なし
2. 実用新案登録 該当なし
3. その他 該当なし
