http://repub.eur.nl/res/aut/45774/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/30412/ 2008-05-03T00:00:00Z Laboratory diagnosis for DNA repair diseases has been performed in western Europe from the early seventies for xeroderma pigmentosum (XP) and from the mid-eighties for Cockayne syndrome (CS) and trichothiodystrophy (TTD). The combined data from the DNA repair diagnostic centres in France, (West) Germany, Italy, the Netherlands and the United Kingdom have been investigated for three groups of diseases: XP (including XP-variant), CS (including XP/CS complex) and TTD. Incidences in western Europe were for the first time established at 2.3 per million livebirths for XP, 2.7 per million for CS and 1.2 per million for TTD. As immigrant populations were disproportionately represented in the patients' groups, incidences were also established for the autochthonic western European population at: 0.9 per million for XP, 1.8 per million for CS and 1.1 per million for TTD. Perhaps contrary to general conceptions, compared to XP the incidence of CS appears to be somewhat higher and the incidence of TTD to be quite similar in the native West-European population. http://repub.eur.nl/res/pub/36714/ 2007-01-01T00:00:00Z Trichothiodystrophy (TTD) is a rare autosomal recessive disorder whose defining feature is brittle hair. Associated clinical symptoms include physical and mental retardation of different severity, ichthyosis, premature aging, and, in half of the patients, photosensitivity. Recently, C7orf11 (TTDN1) was identified as the first disease gene for the nonphotosensitive form of TTD, being mutated in two unrelated cases and in an Amish kindred. We have evaluated the involvement of TTDN1 in 44 unrelated nonphotosensitive TTD cases of different geographic origin and with different disease severity. Mutations were found in six patients, five of whom are homozygous and one of whom is a compound heterozygote. All five identified mutations are deletions that have not been described before. Three are deletions of a few bases, resulting in frameshifts and premature termination codons. The other two include the whole TTDN1 gene, suggesting that TTDN1 is not essential for cell proliferation and viability. The severity of the clinical features does not correlate with the type of mutation, indicating that other factors besides TTDN1 mutations influence the severity of the disorder. Since only a small proportion of the analyzed cases were mutated in TTDN1, the nonphotosensitive form of TTD is genetically heterogeneous. Mutations in TTDN1 do not affect the response to ultraviolet (UV) light or the steady state level of the repair/transcription factor IIH (TFIIH), which is central to the onset of the photosensitive form of TTD.