ICNC Abstracts, ICNC 2018

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Genomic analysis identifies pathogenic variants in 9 of 17 cases with full-term cerebral palsy
Yusuke Takezawa, Atsuo Kikuchi, Kazuhiro Haginoya, Tetsuya Niihori, Yurika Numata-Uematsu, Takehiko Inui, Saeko Yamamura-Suzuki, Takuya Miyabayashi, Mai Anzai, Sato Suzuki-Muromoto, Yukimune Okubo, Wakaba Endo, Noriko Togashi, Yasuko Kobayashi, Akira Onuma, Ryo Funayama, Matsuyuki Shirota, Keiko Nakayama, Yoko Aoki, Shigeo Kure

Last modified: 2018-09-12


Introduction: Cerebral palsy (CP) is a common, heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent studies have suggested CP patients include more pathogenic variants than previously expected. We hypothesized that two simple criteria, i.e., full-term births and nonspecific brain MRI findings, are keys to extracting pathogenic variants among cerebral palsy cases due to the following: (i) preterm infants are susceptible to multiple environmental factors and therefore demonstrate an increased risk of CP and (ii) brain MRI assessment is essential for excluding environmental causes and other particular disorders. Methods:A total of 107 patients—all full-term-births—without specific findings on brain MRI were identified among 897 patients diagnosed with CP who were followed at our center. DNA samples were available for 17 of the 107 cases for trio whole-exome sequencing and array comparative genomic hybridization. We prioritized variants in genes known to be relevant in neurodevelopmental diseases and evaluated their pathogenicity according to the American College of Medical Genetics guidelines.Results:Pathogenic/likely pathogenic candidate variants were identified in 9 of 17 cases (52.9%) within eight genes: CTNNB1, CYP2U1, SPAST, GNAO1, CACNA1A, AMPD2, STXBP1, and SCN2A. No pathogenic copy number variations were identified.Conclusion: Our study showed the possibility that a subset of CP patients categorized by two simple criteria (full-term births and nonspecific brain MRI findings) include pathogenic variants despite several limitations. Further genetic investigations of larger cohorts of CP patients are required to help support our results. This could eventually aid the further characterization of the molecular mechanisms of CP.


full-term cerebral palsy; whole exome sequencing; chromosome microarray analysis

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