| Project/Area Number |
16K21079
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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
Pediatrics
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
NAGATA EIKO 浜松医科大学, 医学部附属病院, 特任講師 (90535569)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 臨床遺伝学 / 希少疾患 / ヒトゲノム解析 / 先天異常 / 遺伝子解析 / 遺伝学 / ゲノム |
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| Outline of Final Research Achievements |
Split-hand/foot malformation (SHFM) is a clinically and genetically heterogeneous condition. We sequentially performed screening of the previously identified gene mutation, array comparative genomic hybridization, and whole exome sequencing (WES) in recruited 140 Japanese families with nonsyndromic
and syndromic SHFM. Consequently, we identified not only known pathogenic CNVs and rare variants in known causative genes, but also a de novo 19q13.11
deletion disrupting UBA2 and variants that probably affect function in LRP6 and UBA2. Furthermore, the results together with previous data such as the development of SHFM in Lrp6 knockout mice, the presence of SHFM in two subjects with 19q13 deletions involving UBA2, and strong mouse Uba2 expression in the developing limb buds, imply that LRP6 and UBA2 represent plausible candidate genes for SHFM.
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| Academic Significance and Societal Importance of the Research Achievements |
裂手裂足症は、単独で発症するタイプと、裂手裂足症＋脛骨形成不全や裂手裂足症＋大腿骨形成不全などの関連疾患の一部の表現型として発症するタイプに大別される。我々は現在までに140家系以上のSHFM、SHFLD、GWCの患者を集積した。計画通りに進め、時に分子遺伝学的解析手法に関して、連携協力者と協力して研究を遂行した。次世代シーケンサーの遺伝子解析、マウス等の解析において、いくつかの遺伝子を同定し、最終年度の成果では、新規のSHFMの候補遺伝子として、LRP6およびUBA2が可能性があることを見出した。今後これらの候補遺伝子を研究することによって四肢および指趾の再生医療等に貢献する可能性がある。
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