20.500.12556/DiRROS-24234 Unravelling genetic etiology of cerebral palsy findings from a Slovenian pediatric cohort Introduction: Cerebral palsy (CP) is a permanent movement or postural disorder due to non-progressive injury to the developing brain, with recent research suggesting a genetic contribution in many patients. This study aimed to investigate the genetic etiology of CP in Slovene children without a previously suspected genetic cause or with prior negative genetic testing. Methods: All children born after 2003 from the Slovenian National Registry of Cerebral Palsy (SRCP) without an established genetic diagnosis were invited to participate in this cross-sectional study. Whole exome sequencing (WES) was conducted, followed by analysis of 110 CP-associated genes. Thirteen patients underwent additional family segregation by Sanger sequencing. Genetic findings were classified according to the ACMG guidelines. Results: The study included 136 children, of whom 68 (50%) were male. Spastic CP was identified in 85% of the participants, dyskinetic in 13%, and ataxic in 2%. Gross Motor Function Classification System (GMFCS) levels varied, with the majority (36%) classified as level I. Pathogenic variants, likely pathogenic variants, or ‘de novo’ variants of unknown significance (VUS) were identified in nine children (6.6%) in ATL1, CTNNB1, DYRK1, KMT2A, PROC, SPAST, ZC4H2, and ZSWIM6. Among these nine children, two had normal brain Magnetic Resonance Imaging (MRI) and three had an unsuspicious medical history. Conclusion: This study identified plausible, possible, or definite genetic etiologies in a cohort of children with CP. Apart from the exclusion of individuals with a previously established genetic diagnosis, no other selection criteria were applied, allowing for an inclusive assessment of genetic contributions within this population. With the advent of personalized medicine and genetic treatment, understanding the genetic underpinnings of CP is crucial for targeted therapy. cerebral palsy genetic etiology whole exome sequencing gene therapy CTNNB1 true false true Angleški jezik Ni določen Neznano 2025-11-21 14:03:52 2025-11-21 14:03:52 2025-11-22 03:57:14 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 28. 7. 2025; str. 1-11 Vol. 16 [article no.] ǂ1615449 2025 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 616.8:616-053.2 1664-2295 10.3389/fneur.2025.1615449 243989251 RAZ_Arkar_Silan_Ula_2025.pdf RAZ_Arkar_Silan_Ula_2025.pdf 1 CE103523BDECA9DE7823448E2E2BB2C8 6cafabed99a395462b66ec475df61e56feb178280d61b7d2c065848449d06ba1 a801ff9a-c6da-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36091 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1615449/full 0 b4ebb393-c6da-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36092 Univerzitetni klinični center Ljubljana 0 0 0