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Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene

journal contribution
posted on 2023-06-08, 08:17 authored by Bernard C Broughton, Mark Berneburg, Heather Fawcett, Elaine M Taylor, Colin F Arlett, Tiziana Nardo, Miria Stefanini, Emory Menefee, Vera H Price, Sophie Queille, Alain Sarasin, Elisabeth Bohnert, Jean Krutmann, Rosemarie Davidson, Kenneth H Kraemer, Alan LehmannAlan Lehmann
The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription factor TFIIH with DNA helicase activity. TFIIH has two functions, in basal transcription and nucleotide excision repair. Mutations in XPD that affect DNA repair but not transcription result in the skin cancer-prone disorder, xeroderma pigmentosum (XP). If transcription is also affected, the result is the multi-system disorder trichothiodystrophy (TTD), in which there is no skin cancer predisposition, or in rare cases, XP combined with Cockayne syndrome. Up till now there have been no reports of combined clinical features of XP and TTD. We have now identified two patients with some features of both these disorders. One of these, XP189MA, a 3-year-old girl with sun sensitivity, mental and physical developmental delay, has XPD mutations not previously reported, and barely detectable levels of nucleotide excision repair. The other, XP38BR, a 28-year-old woman with sun sensitivity, pigmentation changes and skin cancers typical of XP, has a mutation that has been identified previously, but only in TTD patients with no features of XP. The level of repair of UV damage in XP38BR is substantially higher than that in other patients with the same mutation. With both patients, polarized light microscopy revealed a `tiger-tail¿ appearance of the hair, and amino acid analysis of the hairshafts show levels of sulfur-containing proteins intermediate between those of normal and TTD individuals. Our findings highlight the complexities of genotype¿phenotype relationships in the XPD gene.

History

Publication status

  • Published

Journal

Human Molecular Genetics

ISSN

0964-6906

Issue

22

Volume

10

Page range

2539-2547

Pages

9.0

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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