NSD1 mutations in Sotos Syndrome induce differential expression of long non-coding RNAs, miR646 and genes controlling the G2/M checkpoint

An increasing amount of evidence indicates the critical role of NSD1 gene in the Sotos syndrome (SoS) and tumor. Molecular mechanisms affected by NSD1 mutations are largely uncharacterized. In order to assess the impact of NSD1 haploinsufficiency in the pathogenesis of SoS, we analyzed the gene expression profile of fibroblasts isolated from the skin sample of 15 SoS patients and from 5 healthy parents. We identified 7 differentially expressed genes and 5 differentially expressed non-coding RNAs. The most up-regulated mRNA was stratifin (SFN) (fold change, 3.9, p<0.05) and the most down-regulated mRNA was goosecoid homeobox (GSC) (fold change, 3.9, p<0.05). Fifteen individuals with classical clinical features of SoS and with the molecular diagnoses of NSD1 pathogenic variants (point mutation or deletion) were enrolled in the study. Were also enrolled five parents, of the same sex of the correspective SoS patient, as controls selected on the basis of skin biopsy availability.