Due to the limitation in access to patients’ tissues where the PAH gene is expressed (liver and to a lesser extent, kidney) the splicing defect was studied using minigenes and in a gene edited HepG2 cell line homozygous for the c.1066-11G>A variant, in which almost no detectable PAH protein and activity were observed. The gene discussed is PAH; the disease is pulmonary arterial hypertension.