[P3-61] Comprehensive genetic analysis in West syndrome and Ohtahara syndrome: a single center study
[Introduction] West syndrome and Ohtahara syndrome are a continuum of early onset epileptic encephalopathies (EOEEs). Recent genetic studies have elucidated causative roles for genetic abnormalities in EOEEs. In this study, we investigated the underlying genetic causes in patients with West syndrome and Ohtahara syndrome.
[Methodology] Patients were recruited from Nishi-Niigata Chuo National hospital between 2004 and 2016. 32 patients (28 of West syndrome and four of Ohtahara syndrome), who had severe developmental delay, unknown etiology, no chromosomal abnormality in G-band, and no cortical malformation on MRI, were included in this study. We performed candidate gene analysis in eight patients for ARX, STXBP1, SPTAN1, or SCN2A by high-resolution melting analysis or PCR direct sequence. In four patients, target capture and sequencing against 38 genes were performed. Whole exome sequence was performed in 18 patients including three patients with negative results of target sequencing. Chromosomal microarray analysis was performed in six patients.
[Results] We identified pathogenic mutation in 11 genes (ARX, CDLK5, STXBP1, SPTAN1, GNAO1, SCN2A, CASK, ALG13, EEF1A2, TBL1XR1 and SETD5) in 16 of 30 patients (53%). In two patients, we identified submicroscopic chromosomal deletion in 9q33.3q34.1 and 14q13.1q13.3. No mutations in known causative gene were found in the remaining 14 patients.
[Conclusions] We found pathogenic genetic alterations in 18 of 32 patients (56%). Genetic backgrounds of EOEEs are heterogeneous. Our results in a single center may reflect the current state of genetic background of EOEEs. Further accumulation of patients with precise clinical evaluation will facilitate genotype–phenotype correlation in EOEEs.
[Methodology] Patients were recruited from Nishi-Niigata Chuo National hospital between 2004 and 2016. 32 patients (28 of West syndrome and four of Ohtahara syndrome), who had severe developmental delay, unknown etiology, no chromosomal abnormality in G-band, and no cortical malformation on MRI, were included in this study. We performed candidate gene analysis in eight patients for ARX, STXBP1, SPTAN1, or SCN2A by high-resolution melting analysis or PCR direct sequence. In four patients, target capture and sequencing against 38 genes were performed. Whole exome sequence was performed in 18 patients including three patients with negative results of target sequencing. Chromosomal microarray analysis was performed in six patients.
[Results] We identified pathogenic mutation in 11 genes (ARX, CDLK5, STXBP1, SPTAN1, GNAO1, SCN2A, CASK, ALG13, EEF1A2, TBL1XR1 and SETD5) in 16 of 30 patients (53%). In two patients, we identified submicroscopic chromosomal deletion in 9q33.3q34.1 and 14q13.1q13.3. No mutations in known causative gene were found in the remaining 14 patients.
[Conclusions] We found pathogenic genetic alterations in 18 of 32 patients (56%). Genetic backgrounds of EOEEs are heterogeneous. Our results in a single center may reflect the current state of genetic background of EOEEs. Further accumulation of patients with precise clinical evaluation will facilitate genotype–phenotype correlation in EOEEs.