Exon-skipping and genetic compensation due to biallelic mutations in the neurodevelopmental disease gene LNPK

The preprint operates within the dominant paradigm of molecular genetics and genomics, specifically focusing on the established understanding of gene mutations, RNA processing, and protein synthesis. It also adheres to the broader paradigm of Mendelian inheritance in explaining disease etiology.

This preprint investigates the functional impact of novel variants in the LNPK gene, associated with neurodevelopmental disorders. The research follows established methodologies (RT-qPCR, Western blotting, Sanger sequencing, NMD inhibition) within the existing paradigm of molecular genetics. The study confirms the pathogenicity of the variants by demonstrating their disruptive effect on RNA splicing, leading to reduced protein levels, consistent with the current understanding of LNPK's role in neuronal development. The investigation of a genetic compensation mechanism further adheres to established principles within the field. While the genetic compensation finding is novel in the context of LNPK, it does not challenge the existing paradigm but rather refines our understanding within it. Therefore, this work fits squarely within the "Normal Science" stage of Kuhn's cycle, as it contributes to the existing body of knowledge without proposing a radical shift in understanding or methodology.