Akademik Veri Yönetim Sistemi
American Journal of Medical Genetics, Part A, cilt.200, sa.5, ss.1145-1150, 2026 (SCI-Expanded, Scopus)
Pathogenic variants in NCKAP1, a gene encoding a core component of the WAVE regulatory complex (WRC), have recently been implicated in neurodevelopmental disorders (NDDs), but the clinical spectrum remains incompletely characterized. We describe a father and daughter carrying a novel heterozygous NCKAP1 splice-site variant (c.2021+1G>A), both presenting with developmental delay, autistic features, epilepsy, and shared craniofacial dysmorphisms. Although familial cases have been previously reported, this is the first to present thorough phenotypic documentation, including longitudinal neurodevelopmental and neuroimaging follow-up, dermatologic involvement, and dysmorphic evaluation in both the parent and the child. Notably, both individuals showed nail dystrophy and inflammatory skin lesions, expanding the phenotypic range of NCKAP1-related disorders beyond the nervous system. Comparative analysis revealed significant overlap with reported features of RAC1, CYFIP2, and WASF1-related syndromes, genes that also encode components of the WRC, further supporting a shared pathophysiological mechanism involving cytoskeletal dysregulation. Expression data from GTEx and HPA confirm that NCKAP1 is not only neuronally expressed but also found in epithelial tissues, providing biological plausibility for the dermatologic manifestations. This report contributes new clinical insights into NCKAP1-associated NDDs and emphasizes the importance of detailed phenotyping in rare familial cases to refine gene-disease associations.