Many DNA repair deficient diseases can subsequently lead
to accelerated ageing, a prime example of this can be seen in Trichothiodystrophy (1). Trichothiodystrophy, commonly
shortened to TTD is an uncommon genetic disorder (with an incidence rate of
about 1 in 1 million new born infants in the USA and Europe) that has the
distinctive features of short, brittle hair along with an abnormally low sulphur
content in the body (which is what makes hair brittle, as sulphur is an
essential mineral which gives hair its strength) (2 and 3). Symptoms include
dark scaly patches on the skin around the body, which burns very easily (4). Mild
cases may only involve brittle hair, but more severe cases can lead to
intellectual disabilities, stunted growth and reoccurring respiratory
infections, with many patients dying at younger ages (3). The central nervous
system (CNS) can also be affected by lack of muscle coordination, seizures and tremors
(4). In very few cases (less than 1% of occurrences) cataracts is also synonymous
with the disorder (4). Approximately half of the patients suffering from TTD
also experience extreme photosensitivity which further classifies its syndromes
into 4 subdivisions, BIDS, PBIDS, IPBIDS and IBIDS (5). The photosensitivity is
as a result of a fault in their Nucleotide Excision Repair pathway, as it
doesn’t remove ultra violet induced DNA lesions efficiently (6). Presently, there
are only 4 genes known to us that can lead to the TTD phenotype, namely TTDN1,
XPB, XPD, TTDA (however, mutation of the latter 3 genes are the only ones that
lead to photosensitivity) (5). Proteins that are transcribed from these genes
have a mutually beneficial relationship as they become part of a group along
with p52, p62, p44 and p34, known as the general transcription factor (TFIIH)
complex, which in turn is involved in the repair of DNA damage (3). From this,
we can deduce that mutations in the XPB, XPD or TTDA genes reduce the total
amount of TFIIH complex within cells which in turn impairs transcription of
proteins and DNA repair. Mutations of the TTDN1 as previously mentioned, lead
to the non-photosensitive variation of TTD account for 18% of all cases of
non-photosensitive TTD and not a lot more is known about the gene (3). The core
of the TFIIH complex forms a ring-shaped structure, connected to cdk activating
kinase. The TFIIH complex the located the lesion, and supports the excision of
the affected area with the use of specific endonuclease enzymes (7). The ATPase
activity involved in XPB and XPD are necessary in the removal of DNA lesions
(the p52 even interacts with XPB to help stimulate its ATPase activity (7). Trichothiodystrophy is known as an autosomal recessive disease, so all copies of
the gene in each cell has the mutations (3). Parents typically don’t display signs
or symptoms of the condition, but each do carry a copy of the mutated gene (3).

In eukaryotes, NER needs around 28 proteins to target the DNA that suffers from
damage, recognition of that damage, opening of the DNA around the lesion and
finally, gap filling DNA synthesis and ligation (7). There is currently no cure
available for TTD. However, there are several methods used to help sufferers of
the disorder live longer and more fulfilling lives. In particular protection
from the sun using protective clothing and sun screen can help prevent sun
induced skin damage, especially in patients suffering from photosensitive
variants of the disease (8). Scientists have also recently concluded that
dietary cytosine supplementation can also help lessen the effects of the
disease on stunted grown and intellectual disabilities (as cytosine is crucial
in the polynucleotide chain of RNA/DNA (8). Regular physical therapy can help strengthen
muscles and physiological and social support is recommended for patients (9).

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now