Table 1.

XP and related disorders

Disease	Gene	Protein function	Defective pathway	Clinical features
Xeroderma pigmentosum	XPA XPB/ERCC3 XPC XPD/ERCC2 XPE/DDB2 XPF/ERCC4 XPG/ERCC5 XPV/POLH	Damage verification Helicase Damage recognition Helicase Damage recognition Nuclease Nuclease Polymerase	NER NER NER NER NER NER NER Translesion synthesis	40% of the patients show extreme sensitivity to sunlight and sunburn reaction, while 60% do not show any sunburn reaction. 20/30% of the patients show neurological abnormalities: neuronal degeneration resulting in deafness, ataxia, areflexia, microcephaly and intellectual deficiency and impaired eye sight. XPC, XPE and XPV do not show signs of neurological abnormalities. (Lehmann et al., 2011; Fassihi et al., 2016)
Cockayne syndrome	CSA/ERCC8 CSB/ERCC6	Damage recognition and Ubiquitination Damage recognition	TC‐NER (transcription‐coupled NER)	Microcephaly, ataxia, failure to thrive and delayed development. Increased sensitivity to sunlight (photosensitivity), and in some cases, even a small amount of sun exposure can cause a sunburn or blistering of the skin. Hearing loss, vision loss, severe tooth decay, bone abnormalities, abnormal thermoregulation in hands and feet and liver dysfunction.(Rapin et al., 2006; Wilson et al., 2016)
Ataxia telangiectasia	ATM	Damage‐activated protein kinase	DSB (DNA double strand‐break)	Ataxia, chorea, myoclonus neuropathy. Slurred speech and oculomotor apraxia. Small clusters of enlarged blood vessels called telangiectases, which occur in the eyes and on the surface of the skin, are also characteristic of this condition.High amounts of a protein called α‐fetoprotein (AFP) in the blood.
Ataxia with oculomotor apraxia type 1	–	DNA‐adenylate hydrolase	SSB (DNA single‐strand Break)	Ataxia, oculomotor apraxia and peripheral vision. (Clements et al., 2004)
Ataxia with oculomotor apraxia type 2	–	DNA–RNA helicase	SSB	Ataxia, oculomotor apraxia and peripheral vision. High amounts of a protein AFP in blood. (Clements et al., 2004)
Spinocerebellar ataxia with axonal neuropathy	–	Tyrosyl phosphodieaterase involved in SSB repair	SSB	Spinocerebellar ataxia with axonal neuropathy.El‐Khamisy et al., 2005)
RIDDLE syndrome	–	Ubiquitination	DSB	Microencephaly, facial dysmorphism, telangeiectasia, pulmonary fibrosis, learning difficulties and ataxia. (Stewart et al., 2009)