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Similar Post-UV Cell Survival of Fibroblasts from Photosensitive and non-Photosensitive Trichothiodystrophy Patients with Defects in the DNA Helicase XPD Gene

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • S. G. Khan
  • J. Boyle
  • T. Ueda
  • D. Tamura
  • J. J. DiGiovanna
  • K. H. Kraemer


We studied trichothiodystrophy (TTD) to examine the role of DNA repair genes in skin sun-photosensitivity. TTD is a rare, autosomal recessive disorder with a wide spectrum of clinical manifestations and defects in DNA repair/transcription genes (XPD, XPB, p8/TTDA) or in TTDN1, a gene with unknown function. We describe 8 TTD patients (age 1.5 to 9 yr) from 6 families with defects in XPD DNA helicase (XPD-TTD). These patients were XPD compound-heterozygotes and each had at least one missense mutation. All of the patients had abnormal hair (brittle hair, hair shaft defects, and tiger tail banding), short stature, microcephaly, low birth weight, and intellectual impairment. In line with other XPD-TTD patients, 3 were photosensitive. Interestingly, 5 patients from 3 different families were non-photosensitive. Three missense mutations (p.Q726E, p.L399F, and p.A725P) in these patients were associated with non-photosensitivity. The pQ726E mutation had residual DNA repair activity as measured by host cell reactivation and comet assays. The post-UV cell survival of fibroblasts from non-photosensitive is less than from photosensitive patients. These results suggest that the fibroblast cell killing is dissociated from clinical photosensitivity in the TTD patients and some missense mutations with partial DNA repair function may protect the non-photosensitive patients from sunburning.

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