| Project/Area Number |
23390249
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
FUKAMI MAKI 独立行政法人国立成育医療研究センター, その他部局等, その他 (40265872)
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| Co-Investigator(Kenkyū-buntansha) |
SONEDA Shun 独立行政法人国立成育医療研究センター, 分子内分泌研究部, 研究員 (10367378)
KATO Fumiko 浜松医科大学, 小児科, 研究員 (10462798)
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| Project Period (FY) |
2011-11-18 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | 遺伝子 / ホルモン / 先天疾患 / 性分化 / 小児内分泌学 |
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| Research Abstract |
The aim of the present study was to clarify the molecular basis of reproduction failure. We performed systematic mutation screening and genome-wide copy number analyses for patients with disorders of sex development (DSD), gonadotropin deficiency, and precocious puberty. Our results include; 1) Mutations in known causative genes account for only a small fraction of the etiology of 46,XY DSD and gonadotropin deficiency. 2) FGF8 haploinsufficiency may underlie thyroid dysfunction and cardiac anomalies. 3) Cryptic genomic rearrangements constitute rare causes of 46,XY, DSD. 4) Genomic rearrangements leading to aromatase excess syndrome (AEXS) are caused by recombination- and replication-based mechanisms. 5) Hypogonadism in patients with AEXS is ascribed to the negative-feedback effect of estrogens on FSH secretion. 6) Adrenal androgens serve as the major source of estrogens in prepubertal patients with AEXS. 7) SOX2 mutations are associated with a broad phenotypic variation.
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