2018 Fiscal Year Final Research Report
molecular basis and a new genetic cause of primary aderenal insufficiency
Project/Area Number |
16K09998
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | Keio University |
Principal Investigator |
Amano Naoko 慶應義塾大学, 医学部(信濃町), 共同研究員 (70348689)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Keywords | 副腎機能低下症 |
Outline of Final Research Achievements |
We enrolled 63 Japanese children (59 families) with biochemically uncharacterized PAI, and sequenced 12 PAI-associated genes. We calculated the proportion of mutation-carrying patients according to demographic characteristics. We identified genetic defects in 50 (85%) families: STAR in 19, NR0B1 in 18, SAMD9 in seven, AAAS in two, NNT in two, MC2R in one and CDKN1C in one. This work was published in the peer-reviewed academic journal‘European journal of endocrinology.’ We identified submicroscopic deletions in the gene A in three patients with adrenal hypoplasia. The in vitro study using the HEK293 cells having stable expression of gene A revealed that β-catenin producing-capacity would decrease in the identified gene A-deleted cells.
|
Free Research Field |
小児内分泌
|
Academic Significance and Societal Importance of the Research Achievements |
本邦おける「生化学診断が困難な原発性副腎皮質機能低下症」の分子基盤および各単一遺伝子疾患の臨床的特徴を明らかとした。さらに先天性副腎低形成症の新規責任遺伝子を発見し、その分子機構がWnt-βカテニンシグナル系の低下であることを明らかにする。最終的にはヒトの副腎発生分化におけるWnt-βカテニンシグナル系の意義を解明することが目標である。
|