| Project/Area Number |
17591063
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Hokkaido University |
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Principal Investigator |
TAJIMA Toshihiro Hokkaido Uni., Grad.School of Med., Lec., 大学院医学研究科, 講師 (50333597)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOHARA Nobuo Hokkaido Uni., Hokkaido Uni.Hospital., Lec., 大学病院, 講師 (90250422)
SYGAWARA Teruo Hokkaido Uni., Grad.School of Med., Inst., 大学院医学研究科, 助手 (40250451)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Adrenal / Gonad / NR5A1 / Mineralocorticoid / Bartter syndrome / 性腺 / NR5Al / ミネラルコルチコイド / 過形成 / 再生 |
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| Research Abstract |
Ad4/BP (NR5A1) regulates multiple genes involved in the adrenal and gonadal development and in the biosynthesis of a variety of hormones. We identified a novel mutation of the NR5A1 gene in an 18-yr-old Japanese patient with 46, XY karyotype. A heterozygous G to T transversion in exon 3 lead to the missense mutation (V41G). This amino acid is conserved among mouse, rat, bovine and human Ad4/BP and is located in the DNA-binding region. It is speculated that this mutation might affect DNA-binding. This must be further studied.
It has been proved that P450 oxidoreductase (POR) deficiency causes disordered steroidogenesis. We identified a new patient with a missense mutation of R457 H in the POR gene. This patient showed mild skeletal symptoms and the molecular mechanism is now analyzed.
Mutations of MRAP, an interacting partner of the ACTH receptor, are one of causes of familial glucocorticoid deficiency. We analyzed ACTH receptor and MRAP genes in three patients of glucocorticoid deficiency. However, we did not identify any mutation in both genes.
Bartter syndrome (BS) is one of the most frequent inherited tubulopathy, characterized by urinary potassium loss and metabolic alkalosis. Antenatal (or neonatal) Bartter syndrome is caused by homozygous or compound heterozygous mutations in the SLC12A1 gene (NKCC2). Classic Bartter syndrome is caused by deletions or mutations of the CLCNKB gene.
In two patients with neonatal Bartter syndrome, four novel mutations: N117X, G257S, 0792fs, and N984fs were identified. In classic type, a large deletion, a partial deletion and two mutations (Δ L130 in exon 4 and W610X in exon 16) were identified.
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