Novel homozygous missense variants in associated with neurodevelopmental disorder: Clinical and pathogenetic research.

Background: Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia (NEDSCAC), induced by gene, is an autosomal recessive rare disorder characterized by widespread developmental delay with varying degrees of intellectual impairment. Other symptoms include limb spasticity, cataracts, and cerebellar hypoplasia. So far there have been limited reports on NEDSCAC.

Methods: In this study, we conducted genetic testing on a child presenting with developmental delay as the primary clinical feature. The genetic test results indicated the presence of novel homozygous missense variants c.74G > A, p.(Arg25His) in the gene. functional validation experiments, including plasmid construction and cell transfection, Western blotting, and molecular dynamics structural modeling, were performed on the MED27 Arg25His variant.

Results: The results demonstrated a significant reduction in protein expression of MED27 Arg25His and indicated may weaken the interaction force between the MED27 subunit and MED14 subunit.

Conclusions: This study expands our understanding of gene variants and their associated clinical phenotypes. Additionally, it contributes to the investigation of the potential pathogenesis of NEDSCAC caused by gene variants.