The development of the molecular mechanism and treatment methods of Schaaf-Yang syndrome focusing on protein transport disorders

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17308
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nagoya City University
• Principal Investigator: HORI IKUMI 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00745929)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Schaaf-Yang症候群

Outline of Final Research Achievements

The purpose of this study is to establish the clinical feature of Schaaf-Yang syndrome (SYS) by focusing on protein transport and to elucidate the molecular mechanism. Regarding patient accumulation, we conducted a national survey of SYS in Japan and created a patient registry.
Transgenic mice (Tg mice) and knockout (KO) mice has been created. Tg mice were embryonic lethal, but the phenotype of KO mice remained minimal. Based on the hypothesis that the effect on MAGEL2 differs depending on the type of mutation, we are creating a cell line library in vitro in which various mutations of MAGEL2 are introduced.

Free Research Field

小児神経

Academic Significance and Societal Importance of the Research Achievements

Schaaf-Yang症候群 (SHFYNG) はMAGEL2の短縮変異が原因である。重度の知的障害を示し関節拘縮や脳症の合併を認める。しかし、MAGEL2の短縮型変異がSHFYNGを発症させる分子経路メカニズムはいまだに解明されておらず、本研究は分子機構の解明に一歩近づいたと考えられる。蛋白輸送経路障害を中心としたSHFYNGの発症機序を解明することで、自閉症、パーキンソン病やアルツハイマー病などの神経変性疾患の分子機構の解明につながり、治療法開発の基盤となる。