Generation of human induced pluripotent stem cell lines carrying a heterozygous and homozygous PRKD1 c.1774G > A genetic variant causing syndromic congenital defects

Abstract

Protein kinase D1 (PRKD1) is a serine threonine kinase with roles in the regulation of embryonic development, contractility, vesicle transport and cytoskeleton organization. Consequently, variants in PRKD1 that alter its kinase activity are associated with severe anomalies, manifesting as syndromic congenital defects in patients. To investigate the molecular pathomechanisms underlying PRKD1 genetic variants, the patient-derived PRKD1 p.G592R (c.1774 G > A) mutation was introduced in heterozygous and homozygous configuration into the human induced pluripotent stem cell line (AICS-0031-035:WTC-mTagRFPT-TUBA1B) with CRISPR/Cas9 technology and were thoroughly validated. These hiPSC lines constitute a valuable platform for dissecting the molecular consequences of impaired PRKD1 signaling.