Journal Article

Mutations in the general transcription factor TFIIH result in <b>β</b>-thalassaemia in individuals with trichothiodystrophy

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 R. Lehmann and Douglas R. Higgs

in Human Molecular Genetics

Volume 10, issue 24, pages 2797-2802
Published in print November 2001 | ISSN: 0964-6906
Published online November 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.24.2797
Mutations in the general transcription factor TFIIH result in β-thalassaemia in individuals with trichothiodystrophy

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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 β-globin genes in these individuals. Eleven TTD patients with characterized mutations in the XPD gene have the haematological features of β-thalassaemia trait, and reduced levels of β-globin synthesis and β-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.

Journal Article.  3686 words.  Illustrated.

Subjects: Genetics and Genomics

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