| Project/Area Number |
17K17693
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human genetics
Medical genome science
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Intellectual disability / Congenital anomalies / Sequencing / Candidate gene / ゲノム / 遺伝学 / 遺伝子 / 医療・福祉 |
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| Outline of Final Research Achievements |
Intellectual disability (ID) and multiple congenital anomalies (MCA) are complex neurodevelopmental disorders affecting 2-3% of the general population. Due to the high genetic heterogeneity, the diagnosis is challenging and remains largely unknown. This project aimed at detecting causative single nucleotide variants in undiagnosed ID/MCA patients previously negative for pathogenic copy number variants, with a focus on identifying novel candidate genes.
Whole-exome sequencing was performed in six parent-child trios, in which causative genes were detected in three cases. In two of the cases, rare mutations in genes that have never been associated to disorders were identified, making them potential novel candidate genes. We joined an international collaboration that had been investigating mutations in one of the novel genes, and this work was able to define a new ID/MCA disorder. Currently, functional assays are being carried out for the second novel candidate gene.
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| Academic Significance and Societal Importance of the Research Achievements |
This research was able to successfully identify the causative gene in 50% of the cases, and more importantly, two novel candidate genes. Besides providing a definitive molecular diagnosis, such results might help to guide treatment and better care of each patient.
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