Trichothiodystrophy, a Human DNA Repair ... - Cancer Research

frequency of carcinoma and melanoma associated with the
disease. The clinical symptoms of XP may result from a com
bination of an enhanced frequency of somatic mutations (e.g..
Ref. 37) and a possible depression of the immune response
following solar exposure of XP patients (38, 39), although the
immunodeficiency is controversial. The implication of this is
that any individual with an XP-like defect in excision-repair
would be expected to exhibit the clinical symptoms of XP. In
the excision-defective TTD patients such as P2 this is mani
festly not the case. The skin symptoms of TTD are quite
different from those of patients with XP group D, and there
are no reports of skin cancer associated with TTD (although
skin cancers are not particularly frequent in young patients
from XP group D; e.g., see Refs. 29 and 30). Conversely XP
patients do not show the sulfur-deficient brittle hair, the ichthyosis,
the short stature or the peculiar facies associated with
TTD. An explanation that the mutation causing one of the
diseases is a deletion extending into the gene responsible for
the other disorder is not consistent with these differences in the
clinical symptoms. If one of the disorders (e.g., TTD) resulted
from a deletion which extended into the XP-D gene, the symp
toms of TTD would be expected to include all the symptoms
of XP. Furthermore cytogenetic analysis has failed to detect
any abnormalities in cells from three TTD patients (40).
TTD and XP-D may therefore be phenotypes of patients with
different defects in the same gene. Very diverse clinical symp
toms resulting from different mutations in the globin genes
have been widely reported for the thalassemias (e.g., see Ref.
41). The eventual cloning of the genes defective in XP-D and
TTD and analysis of the mutations resulting in the two disor
ders should help to unravel the relationships between them.
ACKNOWLEDGMENTS
We are grateful to Dr. Christine Smalley, Selly Oak Hospital, Bir
mingham, for referring patient P3 to us.
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