Authors: Behich Koyutourk , Nese Akcan , Ayla Turgay , Dize Deryali , Mahmut Cerkez Ergoren

Abstract

Background: Baraitser-Winter Syndrome Type 1 (BRWS1) is a developmental disorder with low incidence, characterised by autosomal dominant congenital abnormalities, including intellectual disability, epilepsy, and structural brain malformations. The syndrome results from pathogenic mutations in the ACTB gene that encodes β-actin—a key cytoskeletal protein essential for cell structure and function.

Case Presentation: We report a patient with clinical features of BRWS1. Whole exome sequencing identified a novel heterozygous missense mutation, c.353A>T (p.K118M), in the ACTB gene. The mutation results in the replacement of a conserved lysine with methionine at position 118. According to ACMG guidelines, it was classified as "likely pathogenic." The mutation was not present in population databases and was not reported earlier in HGMD or ClinVar. Parental DNA Sanger sequencing confirmed the variant to be of de novo origin.

Conclusion: This is the first clinical report of the ACTB p.K118M variant associated with BRWS1. The findings expand the mutational spectrum of ACTB and are consistent with a likely pathogenic classification, resulting in improved molecular diagnosis and understanding of the genetic basis of the condition.

Keywords: ACTB, rare disease, Baraitser-Winter syndrome type 1, case report.