Syndromic RNA polymerase II insufficiency: Generation of a human induced pluripotent stem cell line (UUIGPi002A-5) with a heterozygous disruption of POLR2A

Heterozygous variants in POLR2A, encoding the largest subunit of RNA polymerase II, cause severe neurodevelopmental and multisystem abnormalities in humans. Using CRISPR/Cas9 we generated the human iPSC line KICRi002A-5 with a heterozygous truncating 4 bp insertion in exon 5 of the POLR2A gene. Analysis using qRTPCR confirmed reduced POLR2A mRNA in KICRi002A-5 vs. the isogenic WT iPSC line. The edited iPSC line expressed pluripotency markers and exhibited differentiation capacity into the three germ layers. Assessment of genomic integrity revealed a normal karyotype and OFF-target editing was excluded. The iPSC line KICRi002A-5 provides a useful resource to study mechanisms underlying developmental defects caused by RBP1 insufficiency.

Automated summary

Heterozygous variants in the POLR2A gene can cause severe neurodevelopmental abnormalities in humans. The edited iPSC line KICRi002A-5 provides a valuable resource for studying developmental defects caused by RBP1 insufficiency.