Next-Generation Sequencing Unravels the Genetic Landscape of Unexplained Neonatal Seizures in a Chinese Cohort
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Purpose This study aimed to investigate the genetic spectrum of unexplained neonatal seizures in a Chinese population. Methods We retrospectively analyzed 40 neonates with unexplained seizures admitted to a neonatal intensive care unit at a tertiary hospital between 2016 and 2024. Whole-exome sequencing (WES), clinical exome sequencing, trio-WES, and mitochondrial DNA analysis were performed. Results Pathogenic or likely pathogenic variants were detected in 67.5% (27/40) of cases, including, but not limited to, variants in KCNQ2 , ALDH7A1 , and SUOX . Additionally, nine of the 28 identified variants were novel. Although diagnostic yields varied among methodologies, the differences were not significant. A dual diagnosis was identified in one individual with compound heterozygous SUOX mutations and a de novo TUBG1 deletion. Severe phenotypic manifestations were associated with SUOX nonsense or frameshift mutations. Cases responsive to vitamin B6 underscored the potential for precision therapy. Conclusion These results underscore the genetic heterogeneity of neonatal seizures and the role of next-generation sequencing in their diagnosis and management. Early molecular diagnosis could facilitate targeted interventions and genetic counseling.
