Genetic and biochemical analyses of mTOR related megalencephaly

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15530
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Nagoya City University
• Principal Investigator: Saitoh Shinji 名古屋市立大学, 大学院医学研究科, 教授 (00281824)
• Co-Investigator(Kenkyū-buntansha): 中西 真 東京大学, 医科学研究所, 教授 (40217774)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 巨脳症 / mTOR / 次世代シーケンシング

Outline of Final Research Achievements

Next generation sequencing based targeted panel analysis was performed on 28 patients with megalencephaly. We detected a pathogenic mutation in 13 of 27 patients (48.1%) including one patient with a mosaic mutation which was only detected in the affected brain tissue. Western blot analysis using lymphoblastoid cell lines established from peripheral leukocytes with phospho-S6 antibody was performed in 7 mutation-positive patients, and significantly increased phospho-S6 representing abnormal activation of mTOR pathway was found in all 7 patients. Increased phospho-S6 was also detected in 1 of 8 mutation-negative patients. Collectively, our combination of genetic and biochemical analyses is useful for diagnosis of genetic megalencephaly syndromes.

Free Research Field

小児科