3.3. TFIIH and Trichothiodystrophy (TTD)
Trichothiodystrophy (TTD) is another autosomal recessive disorder, caused by mutations within the NER proteins, including TFIIH. TTD is characterized by Sulphur-deficient brittle hair, dry and scaly skin (ichthyosis), congenital cataracts, poor coordination, and skeletal abnormalities (Lehmann, 2001; Stefanini, 2013; Taylor et al., 1997). Despite sensitivity to sunlight, there are no reports of skin cancer or any similarities to the XP group. TTD is considered to be a transcription syndrome. However, it has been noted that TTD does have some repair deficiencies at certain mutation sites, but they are very heterogenous between patients in the severity of repair deficiency (Lehmann, 2001).
There is evidence to support the theory that mutations occurring in different proteins can destabilize the TFIIH complex, inhibiting parts of the function that occur during transcription (Botta et al., 2002; Stefanini, 2013). This inhibition will then cause deficiency in pre-initiation complex (PIC) assembly and the ability for the DNA to be opened for transcription initiation. Different mutations may have the potential to behave differently, depending on where the mutation is located within the protein, which protein in TFIIH is affected, and how this mutation effects the interactions between the individual subunits of the TFIIH complex (Coin et al., 1998; Singh et al., 2015; Taylor et al., 1997). As shown in Table 1 , mutations in XPD, XPB, and p8 subunits have been implicated in TTD.