molecular basis and a new genetic cause of primary aderenal insufficiency

2018 Fiscal Year Final Research Report

• 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。