2023 Fiscal Year Final Research Report

Establishing a new disease concept and developing diagnostic methods for intractable and undiagnosed eye diseases in Japan

Research Project

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Project/Area Number	20K09825
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56060:Ophthalmology-related
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	HOTTA Yoshihiro 浜松医科大学, 医学部, 教授 (90173608)
Co-Investigator(Kenkyū-buntansha)	岩泉守哉浜松医科大学, 医学部, 助教 (60444361)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	難治性未診断疾患 / 遺伝子診断 / CDK9 / NEK1 / RPGRIP1 / Uniparental disomy
Outline of Final Research Achievements	The purpose of this study is to perform genetic diagnosis on patients with intractable, undiagnosed eye diseases in Japan, identify the causative genes, and establish a new concept of the disease. We employed next-generation sequencers to perform genetic diagnosis. We have reported that 1) CDK9 could the causative gene for a new multiple malformation syndrome similar to CHARGE syndrome accompanied by Inherited retinal dystrophy (IRD), 2) IRD without systemic disease caused by NEK1 gene mutations, 3) IRD which could be caused by uniparental disomy, and 4) high frequent pathogenic deletion of the RPGRIP1 gene in Japanese pediatric IRD.We believe that genetic analysis using next-generation sequencers is effective in diagnosing patients with intractable, undiagnosed eye diseases. Genetic counseling requires careful consideration because pediatric IRD includes complex genetic abnormalities such as uniparental disomy.
Free Research Field	眼科学
Academic Significance and Societal Importance of the Research Achievements	眼所見を有しながら通常の医療では診断に至る事が困難な患者(難治性未診断眼疾患患者)は、まれではあるが存在して、患者・患児と家族は苦しんでいる。本研究はわが国の希少・未診断眼疾患患者に対して次世代シーケンサーを用いた遺伝子検査により確定診断を行った。原因遺伝子の同定によって、新たな疾患概念を確立し、新しい表現型を発見することができた。さらに、まれな遺伝子変異を発見し、小児網膜ジストロフィーのわが国における高頻度変異を報告した。本研究によって、苦しんでいた患者の診断が可能になった、また、精緻な遺伝カウンセリングを行うことにつながり、患者・患児に有用な情報を提供することができた。