The xeroderma pigmentosum group D (XPD) helicase subunit of TFIIH functions
in DNA repair and transcription initiation(1,2). Different mutations in XP
D give rise to th ree ultraviolet-sensitive syndromes: the skin cancer-pron
e disorder xeroderma pigmentosum (XP). in which repair of ultraviolet damag
e is affected; and the severe neurodevelopmental conditions Cockayne syndro
me (CS) and trichothiodystrophy (TTD). In the latter two, the basal transcr
iption function of TFIIH is also presumed to be affected(3-5). Here we repo
rt four unusual TTD patients with fever-dependent reversible deterioration
of TTD features such as brittle hair. Cells from these patients show an in
vivo temperature-sensitive defect of transcription and DNA repair due to th
ermo-instability of TFIIH. Our findings reveal the clinical consequences of
impaired basal transcription and mutations in very fundamental processes i
n humans, which previously were only known in lower organisms.