In addition, defects in DNA damage response factors involved in the processing of TOP1-DNA lesions, such as ataxia telangiectasia mutated, TDP1 (tyrosyl-DNA phosphodiesterase 1), Aprataxin and PNKP (polynucleotide kinase phosphatase), are implicated in neurodegenerative genome instability syndromes such as ataxia telangiectasia, spinocerebellar ataxia with axonal neuropathy 1, ataxia with oculomotor apraxia type 1, and microcephaly with early-onset, intractable seizures and developmental delay, respectively15, 16, 17, 18. Here, TDP1 is linked to Global developmental delay.