Unravelling the role of PAX2 mutation in human Focal Segmental Glomerulosclerosis

We performed a genome­wide differential gene expression analysis by Ion AmpliSeqTM Transcriptome sequencing that targets more than 20,000 human genes to gain insights into the genes and pathways involved in the onset of familial steroid-resistant Focal Segmental Glomerulosclerosis (FSGS) driven by the presence of a heterozygous mutation in the PAX2 gene (PAX2G189R/+). Using a stepwise protocol, we differentiated control and PAX2G189R/+ induced pluripotent stem cells into podocytes and we performed whole-transcriptomic analysis on control and patient cells on days 6, 13 and 18 of differentiation. Our data indicated that the PAX2 mutation mainly affects the focal adhesion pathway and the expression of IGF1, a PAX2 target, in adult podocytes that are more susceptible to cell death by environmental triggers. Overall design: Gene expression profiles of CTR and patient cells on days 6, 13 and 18 of differentiation towards podocytes were generated by Ion AmpliSeq Transcriptome sequencing, in duplicate, using Ion Proton Sequencer.