1/23. A temperature-sensitive disorder in basal transcription and dna repair in humans.The xeroderma pigmentosum group D (XPD) helicase subunit of TFIIH functions in dna repair and transcription initiation. Different mutations in XPD give rise to three ultraviolet-sensitive syndromes: the skin cancer-prone disorder xeroderma pigmentosum (XP), in which repair of ultraviolet damage is affected; and the severe neurodevelopmental conditions cockayne syndrome (CS) and trichothiodystrophy (TTD). In the latter two, the basal transcription function of TFIIH is also presumed to be affected. Here we report four unusual TTD patients with fever-dependent reversible deterioration of TTD features such as brittle hair. cells from these patients show an in vivo temperature-sensitive defect of transcription and dna repair due to thermo-instability of TFIIH. Our findings reveal the clinical consequences of impaired basal transcription and mutations in very fundamental processes in humans, which previously were only known in lower organisms.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
2/23. Trichothiodystrophy with severe cardiac and neurological involvement in two sisters.Trichothiodystrophy or sulphur-deficient brittle hair is a clinical marker for several autosomal recessive neurocutaneous syndromes. The typical hair abnormality is frequently associated with many alterations affecting the skin, nervous system, eyes and bones as well as the immune, gonadal and endocrine systems. We report the first cases of dilated cardiomyopathy in two sisters with trichothiodystrophy, leading to cerebral infarction in the younger one. In addition, both suffer from severe hearing impairment, osteosclerosis, and psychomotor retardation with central hypomyelination. CONCLUSION: Severe cardiac involvement and stroke may be associated features of trichothiodystrophy.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
3/23. prenatal diagnosis in a subset of trichothiodystrophy patients defective in dna repair.Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulphur content, and mental and physical retardation. Numerous additional clinical features may be present, producing a very heterogeneous syndrome. Many cases exhibit ichthyosis and photosensitivity. cells from photosensitive TTD patients show reduced dna repair levels similar to those found in xeroderma pigmentosum. TTD patients have a short life expectancy, and no treatment is known or envisaged. We report the prenatal diagnosis of TTD in two French families, based on dna repair measurements in trophoblasts or amniotic cells, with later confirmation by microscopic analysis of the fetal hairs. Although the dna repair defect was less marked in the fetal cells when compared with fibroblasts from the index case, measurement of dna repair by unscheduled DNA synthesis provided unambiguous evidence of defective dna repair in the fetal cells. This method is therefore a suitable prenatal diagnostic test for those TTD families in which a dna repair defect has been identified.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
4/23. Clinical response of alopecia, trichorrhexis nodosa, and dry, scaly skin to zinc supplementation.Two unrelated patients had dry brittle hair, alopecia, trichorrhexis nodosa, dry scaly skin, pigment dyschromia, short stature, and neurosecretory growth hormone deficiency. By means of the zinc tolerance test, patient 1 was shown to have zinc deficiency, whereas no clear zinc deficiency could be demonstrated in patient 2. In both patients, hair and the skin abnormalities responded to oral zinc therapy.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
5/23. Central osteosclerosis with trichothiodystrophy.Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder associated with defects in nucleotide excision repair. We report a 7-year-old boy with TTD due to mutation in the XPD gene. The patient has classic features of this condition, including brittle, sulphur-deficient hair, ichthyosis, growth retardation and developmental delay. In addition, he has radiological evidence of progressive central osteosclerosis. Although similar radiological findings have previously been reported in a small number of patients, this association is not widely recognised. We review the radiological findings in this and other similar cases and discuss the natural history of these bony changes.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
6/23. Trichothiodystrophy: quantification of cysteine in human hair and nails by application of sodium azide-dependent oxidation to cysteic acid.The term "trichothiodystrophy" (TTD) covers several autosomal recessive diseases whose diagnostic hallmark is short, brittle hair low in sulfur and cystine because of impaired synthesis of high-sulfur matrix protein. Clinical symptoms associated with TTD represent a variable range of abnormalities in organs derived from ectoderm and neuroectoderm. Important laboratory tests of the hair for the diagnosis of TTD comprise polarizing microscopy ("tiger-tail" pattern), electron microscopy, and amino acids analysis of hydrolyzed hair with a special focus on cystine. However, only very few institutions determine the amino acid composition of human hair and nail clippings, which requires special sample preparation including hydrolysis. If no special precautions are taken, quantification of cysteine and cystine becomes inaccurate because of decomposition of these residues during hydrolysis. We therefore performed the sample work-up with azide-dependent oxidation which we have for the first time adapted for analysis of hair and nail clippings. With our control and parent data resembling published data on hair and nail samples, we obtained a decreased proportion of cysteine (half cystine, determined as cysteic acid) in materials obtained from a boy with TTD. Clearly, the method for the quantification of cysteine following sodium azide-dependent oxidation is a suitable and rather convenient approach to the quantification of cyst(e)ine and other amino acids in hair and nail proteins, and is a valuable contribution to the diagnosis of TTD.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
7/23. Cerebellar and cerebral atrophy in trichothiodystrophy.Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
8/23. Trichothiodystrophy, a human dna repair disorder with heterogeneity in the cellular response to ultraviolet light.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.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
9/23. xeroderma pigmentosum (complementation group D) mutation is present in patients affected by trichothiodystrophy with photosensitivity.We studied the response to UV irradiation in cells from four patients, from three apparently unrelated families, affected by trichothiodystrophy (TTD). They showed all the symptoms of this rare autosomal recessive disorder (brittle hair with reduced sulfur content, mental and physical retardation, ichthyosis, peculiar face) together with photosensitivity. We found a decreased rate of duplicative DNA synthesis in stimulated lymphocytes, reduced survival in fibroblasts, and very low levels of unscheduled DNA synthesis (UDS) in Go lymphocytes and fibroblasts after UV irradiation. Complementation studies showed that normal values of UDS are restored in heterokaryons obtained by fusion of TTD cells with normal and xeroderma pigmentosum (XP)-complementation group A-cells. In contrast the defect is not complemented by fusion with XP-complementation group D-fibroblasts.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
10/23. An unusual new hair shaft abnormality: "bubble hair".A 16-year-old otherwise healthy girl developed a localized area of brittle, easily broken hairs on the scalp. In addition, the hair appeared to "come out in clumps," and the overall texture of the hair changed from soft and naturally curly to straight and stiff. An unusual hair shaft abnormality was demonstrated by routine light and electron microscopy, for which we can find no report of similar cases. The case and associated findings are presented.- - - - - - - - - - ranking = 1keywords = brittle (Clic here for more details about this article) |
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