title: Trichothiodystrophy, a human DNA repair disorder with heterogeneity in the cellular response to ultraviolet light.
abstract: Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and physical retardation. Some patients are photosensitive. A previous study by Stefanini et al. (Hum. Genet., 74: 107-112, 1986) showed that cells from four photosensitive patients with TTD had a molecular defect in DNA repair, which was not complemented by cells from xeroderma pigmentosum, complementation group D. In a detailed molecular and cellular study of the effects of UV light on cells cultured from three further TTD patients who did not exhibit photosensitivity we have found an array of different responses. In cells from the first patient, survival, excision repair, and DNA and RNA synthesis following UV irradiation were all normal, whereas in cells from the second patient all these responses were similar to those of excision-defective xeroderma pigmentosum (group D) cells. With the third patient, cell survival measured by colony-forming ability was normal following UV irradiation, even though repair synthesis was only 50% of normal and RNA synthesis was severely reduced. The excision-repair defect in these cells was not complemented by other TTD cell strains. These cellular characteristics of patient 3 have not been described previously for any other cell line. The normal survival may be attributed to the finding that the deficiency in excision-repair is confined to early times after irradiation. Our results pose a number of questions about the relationship between the molecular defect in DNA repair and the clinical symptoms of xeroderma pigmentosum and TTD.
authors: MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, United Kingdom.
authors: A R
authors: AR
authors: Lehmann
authors: C F
authors: CF
authors: Arlett
authors: B C
authors: BC
authors: Broughton
authors: S A
authors: SA
authors: Harcourt
authors: H
authors: H
authors: Steingrimsdottir
authors: M
authors: M
authors: Stefanini
authors: A
authors: A
authors: Malcolm
authors: R
authors: R
authors: Taylor
authors: A T
authors: AT
authors: Natarajan
authors: S
authors: S
authors: Green
mesh_terms: D002470:Cell Survival / Q000528:radiation effects*; D002648:Child; D003057:Cockayne Syndrome / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D006201:Hair Diseases / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000150:complications; D008297:Male; D012313:RNA / Q000096:biosynthesis; D012854:Sister Chromatid Exchange; D013455:Sulfur / Q000172:deficiency*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000378:metabolism
chemical_list: D012313:RNA; D013455:Sulfur; D004247:DNA