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Mutations in the general transcription factor TFIIH result in ß-thalassaemia in individuals with trichothiodystrophy

journal contribution
posted on 2023-06-08, 05:49 authored by Vip Viprakasit, Richard J Gibbons, Bernard C Broughton, John L Tolmie, Donald Brown, Peter Lunt, Robin M Winter, Stefano Marinoni, Miria Stefanini, Louise Brueton, Alan LehmannAlan Lehmann, Douglas R Higgs
The transcription factor TFIIH is involved in both basal transcription and DNA repair. Mutations in the XPD helicase component of TFIIH can result in the diverse clinical features associated with xeroderma pigmentosum (XP) and trichothiodystrophy (TTD). It is generally believed that the multi-system abnormalities associated with TTD are the result of a subtle deficiency in basal transcription. However, to date, there has been no clear demonstration of a defect in expression of any specific gene in individuals with these syndromes. Here we show that the specific mutations in XPD that cause TTD result in reduced expression of the ß-globin genes in these individuals. Eleven TTD patients with characterized mutations in the XPD gene have the haematological features of ß-thalassaemia trait, and reduced levels of ß-globin synthesis and ß-globin mRNA. All these parameters were normal in three patients with XP. These findings provide the first evidence for reduced expression of a specific gene in TTD. They support the hypothesis that many of the clinical features of TTD result from inadequate expression of a diverse set of highly expressed genes.

History

Publication status

  • Published

Journal

Human Molecular Genetics

ISSN

0964-6906

Publisher

Oxford University Press

Issue

24

Volume

10

Page range

2797-2802

Pages

6.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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