2018 Fiscal Year Final Research Report
Identification of a new gene for 46,XY disorders of sex development
| Project/Area Number |
16K09817
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Tokyo Metropolitan Children's Medical Center (Department of Clinical Research) |
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Principal Investigator |
Hasegawa Yukihiro 東京都立小児総合医療センター(臨床研究部), なし, その他 (70172898)
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| Co-Investigator(Kenkyū-buntansha) |
加藤 朋子 国立研究開発法人国立成育医療研究センター, システム発生・再生医学研究部, 研究員 (10638802)
高田 修治 国立研究開発法人国立成育医療研究センター, システム発生・再生医学研究部, 部長 (20382856)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 性分化 |
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| Outline of Final Research Achievements |
The purpose of this study is to identify the responsible gene for our human family cases with disorders of sex development, which is presumably a new entity with 46,XY and ovarian tissue. Known genes for disorders of sex development were denied as a responsible gene by using next generation sequencing technique. There are two 46,XY patients, and two non-affected 46,XY adults and two non-affected 46,XX adults. Assuming that persons with a mutation develop or do not develop this DSD disorder in 46,XY or 46,XX, respectively, three genes were candidate for the responsible gene based on the whole Exome sequencing of all the six family members and on the results of In-Silico analysis. We confirmed the expression of the three genes in mouse fetal gonads and knock-out /variant knock-in mouse are being created.
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| Free Research Field |
小児内分泌学
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| Academic Significance and Societal Importance of the Research Achievements |
胎児期の精巣発達に重要な遺伝子として、SRY, SOX９が知られているが、胎児期卵巣の発達は、精巣分化が進まない状況下でのデフォルトパスウエーともいわれ、卵巣発生の初期にSRY, SOX9と同様に重要な意味を持つ遺伝子が存在するかどうかは、現時点で不明である。我々の研究はヒト46,XYの核型をもち、組織学的に精巣成分を認めず、卵巣成分(卵胞)が存在する現在まで報告のない家系症例に関するものである。この家系での遺伝子変異の同定は、胎児卵巣の初期発生の遺伝学的理解の一助になると期待される。
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