In the present paper we have followed through on this approach to interrogate disease associated genotypes in a physiological context by first generating isogenic iPSCs containing a targeted gene mutation mimicking PD (SNCA A53T Homozygous (HO), NCL (GRN R493X Homozygous (HO)) and Rett Syndrome (MECP2 Hemizygous Truncation (HM) knockout (KO). Here, MECP2 is linked to atypical Rett syndrome.