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.