RESULTS OF WHOLE EXOME SEQUENCING IN NEONATES WITH NEONATAL ENCEPHALOPATHY
TL;DR
WES is an effective method for identifying the genetic causes of NE, especially in full-term newborns and in combination with congenital malformations, especially in full-term newborns and in combination with congenital malformations.
Abstract
Objective: to assess the detection rate of monogenic disorders in neonates with encephalopathy using whole-exome sequencing. Materials and Methods. A cohort descriptive study was conducted at the Ural Research Institute for Maternal and Child Health in 2024–2025. Whole-exome sequencing (WES) results from 41 neonates with neonatal encephalopathy (NE) at a gestational age greater than 28 weeks were analyzed. The phenotype was characterized using "major" and "minor" risk criteria for genetic pathology. Congenital malformations were identified in 11 (27%) infants. Results: Genetic variants of varying significance were detected in 7 (17,07%) children included in the study, in 8 genes (PRD1, DNAH5, DOCK7, SDHA, SLC45A2, RS1, KMT2D, TUBA1A). An association of the finding with the clinical phenotype was confirmed in 75% of cases. In 3 (37,5%) patients, the variants were classified as having uncertain clinical significance. In full-term newborns, the frequency of findings was 22,58%, while in premature infants, no significant variants were identified. In children with congenital malformations, the effectiveness of WES was 36,36% versus 10% in those without congenital malformations (p = 0,069). Conclusion . WES is an effective method for identifying the genetic causes of NE, especially in full-term newborns and in combination with congenital malformations. Timely genetic diagnosis is important for clarifying the prognosis for life and health, personalizing treatment.