Study about modifying factors for phenotypes of adrenoleukodystrophy based on the pathophysiology

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16112
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: The University of Tokyo
• Principal Investigator: Matsukawa Takashi 東京大学, 医学部附属病院, 特任助教 (80755760)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 副腎白質ジストロフィー / 遺伝子表現型連関 / 炎症性脱髄 / 神経遺伝

Outline of Final Research Achievements

We performed the analysis of exome data of 108 Adrenoleukodystrophy (ALD) patients. We considered to identify the modifying factors of ALD by comparing the data by each phenotype. We analyzed the exome data focusing on the genes that were related to ABCD1 because the abnormality of ABCD1 related genes seemed to be related to ALD phenotypes. There were no variants which were significantly related to each phenotype.
In addition, as the causative mutations of ALD, we identified not only missense, splicing-site, nonsense, small insertion, small deletion, and small insertion-deletion mutations but also complex mutations such as large duplication and large insertion-deletion mutation. 16 kinds of mutations were novel mutations. The loss-of-function mutations were identified in not only cerebral form patients but also non-cerebral form patients.

Free Research Field

神経遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、副腎白質ジストロフィー(ALD)の臨床をより円滑に行う上で重要な研究成果であったと考える。原因遺伝子ABCD1の遺伝子変異にはサンガーシークエンスでは同定できない複雑な変異があることがわかり、それらを同定可能であったことから、保因者の解析においても有用になると考える。さらに解析を続け、特に予後不良である小児、思春期、成人大脳型ALDの表現型を規定する修飾因子を同定することで、より円滑に造血幹細胞移植の準備を行うことができるようになると考える。