Elucidation of genetic basis for the brain malformations caused by somatic mosaic mutations.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06994
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Yokohama City University
• Principal Investigator: Fujita Atsushi 横浜市立大学, 医学研究科, 特任助手 (20805113)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 体細胞変異 / 単一遺伝子疾患 / ディープシークエンス

Outline of Final Research Achievements

Hypothalamic hamartoma (HH) and focal cortical dysplasia (FCD) are associated with intractable epileptic seizures. In order to identify new causal genes for HH and FCD, we performed comprehensive and precise genetic analyses for the patients.
We identified three new causal genes of HH using next generation sequencing and SNP array. Two of them, KIAA0556、DYNC2H1, are associated with Sonic Hedgehog signaling and cilia as known causal genes in HH, while somatic mutations of PTPN11 which are belonging to RAS/MAPK signaling were also identified and it might suggest a new mechanism involving development of HH.
In FCD, we have not identified any new causal genes using next generation sequencing.

Free Research Field

人類遺伝学

Academic Significance and Societal Importance of the Research Achievements

視床下部過誤腫の発生の原因遺伝子としてソニックヘッジホッグシグナリングや線毛に関連した遺伝子が知られているが、本研究により同定された3つの遺伝子のうち2つはソニックヘッジホッグシグナリングや線毛に関連した遺伝子であった。残りの１つはRAS/MAPKシグナリングに関連した遺伝子であり、視床下部過誤腫の新しい発生機序の可能性が示唆される。