Genetic background of unexplained full-term cerebral palsy

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Haginoya Kazuhiro 東北大学, 医学系研究科, 非常勤講師 (00208414)
• Co-Investigator(Kenkyū-buntansha): 菊池 敦生 東北大学, 大学病院, 助教 (30447156)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 脳性麻痺 / 遺伝子 / 満期産 / MRI / 全エキソーム解析 / 痙性対麻痺 / てんかん性脳症

Outline of Final Research Achievements

We hypothesized that genetics had a stronger influence in the development of cerebral palsy among full-term infants than preterm infants and evaluated the genetic factors involved in this process. A total of 108 full-term-birth patients without specific findings on brain MRI were identified among 897 cerebral palsy patients who were followed at our center. DNA samples were available for 18 of the 108 cases for trio whole-exome sequencing and array comparative genomic hybridization.
Pathogenic/likely pathogenic candidate variants were identified in 9 of 18 cases (50%) within 8 genes: CTNNB1, CYP2U1, SPAST, GNAO1, CACNA1A, AMPD2, STXBP1, and SCN2A. The detection rate (50%) was significantly higher than that of a previous study (14.2%), which suggested that genetic factors have a stronger influence on the etiology of full-term cerebral palsy compared to preterm cerebral palsy.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、多様な背景をもつ脳性麻痺・脳性麻痺様患者において、ある同じ条件に当てはまる患者に対して遺伝学的検査を進める根拠の一つとなる。遺伝子変異が判明した場合、個々の病態にあわせた適切な医療的介入（精密医療:プレシジョン・メディシン）を行えることが期待される。さらには脳性麻痺やそれに酷似する遺伝性疾患全体の将来的な病態解明や治療法の開発の促進に寄与するものと考えられる。