Dysfunction of key components of DNA damage response (DDR) leads to chromosomal instability syndromes which neurological defects are in common.For examples, mutations of ATM, ATR, NBS1 and MRE11 cause Ataxia-Telangiectasia (A-T), Seckel Syndrome, Nijmegen Breakage Syndrome (NBS) and A-T Like Disorder (A-TLD), respectively.A-T and A-TLD are associated with cerebellar degeneration,NBS is characterized with microcephaly and mental retardation.