1/8. Otorhinolaryngological aspects of xeroderma pigmentosum.OBJECTIVE: to evaluate the probable presence of otorhinolaryngological pathology accompanied by head and neck region skin findings in patients with xeroderma pigmentosum. methods: a total of 19 patients with xeroderma pigmentosum were investigated for otorhinolaryngological findings. The patients gave their anamnesis and underwent physical examination, audiological tests and endoscopic examination. RESULTS: various malignancies developed in 14 patients on the sun-exposed areas of the head and neck region. Multiple malignancies were found in six of them. There was no other pathological condition secondary to this rare clinical entity. CONCLUSION: xeroderma pigmentosum causes skin lesions. Some otolaryngological findings such as rhinitis, sinusitis etc. were thought to be coincidental.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/8. Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene.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 hair shafts 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.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/8. xeroderma pigmentosum and lentigo maligna in identical twins.xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis. skin abnormalities result from an inability to repair UV-damaged DNA. Clinically, XP presents with early onset cutaneous changes (severe photosensitivity, actinic keratoses, and telangiectasias) and an increase of developing cutaneous malignancies beginning in early childhood, but lentigo maligna and melanomas are relatively rare. Here we report on homozygote twins in whom there was no positive family history. They showed subnormal physical growth. On ophthalmological examination, both had photophobia and decreased visual acuity. Since birth, several excisions had been performed for skin neoplasms. In one of them a pigmented patch developed over the frontal area which proved to be lentigo maligna and she was referred to a dermato-oncology center. They have been given isotretinoin and physical sunscreen since then. The follow-up period was extended to 2 years and no serious complications occurred from the above treatment. This is an interesting report about XP in twins with the presentation of the rare neoplasm lentigo maligna.- - - - - - - - - - ranking = 2keywords = physical (Clic here for more details about this article) |
4/8. 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 = physical (Clic here for more details about this article) |
5/8. 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 = physical (Clic here for more details about this article) |
6/8. A mild form of xeroderma pigmentosum assigned to complementation group G and its repair heterogeneity.The specific heterodikaryon complementation results allowed us to allocate a 37-year-old female patient with xeroderma pigmentosum (XP31KO) to complementation group G of rare incidence. A mild form of XP31KO as the third group G patient manifested normal skin reaction to phototest, no physical or neuromental abnormalities, and a basal cell epithelioma, in contrast to the reference group G XP2BI. XP31KO cells showed 25% unscheduled DNA synthesis (UDS) after 10 J/m2 UV compared to less than 5% UDS in XP2BI cells and less hypersensitive responses to UV radiation and 4-nitroquinoline-1-oxide killings than did XP2BI cells. Such a repair phenotype of XP31KO presents an intragroup-G heterogeneity.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
7/8. Cutaneous hypermelanosis and intramelanotic lipid droplets.Intramelanocytic lipid droplets have been observed in 12 patients with different types of hypermelanosis of the skin. These include drug-induced hypermelanosis, hypermelanosis secondary to use of physical agents, hypermelanotic morphea, generalized scleroderma with diffuse hypermelanosis, a hyperkeratotic tumor in xeroderma pigmentosum, aberrant mongolian spot, and methoxsalen-ultraviolet-A-induced hypermelanosis. Lipid storage was selectively observed in melanocytes. Most of the melanocytes with lipid vacuoles showed ultrastructural signs of hyperactive melanosome synthesis and certain cytoplasmic abnormalities such as melanosomal autophagic vacuole formation and mitochondrial alterations. The importance and the origin of the lipid droplets remain unclear.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
8/8. A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy.The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carry out excision repair of UV damage. Seven genetically distinct complementation groups (i.e., A-G) have been identified. A large proportion of patients with the unrelated disorder trichothiodystrophy (TTD), which is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV damage. In most of these cases the repair deficiency is in the same complementation group as is XP group D. We report here on cells from a patient, TTD1BR, in which the repair defect complements all known XP groups (including XP-D). Furthermore, microinjection of various cloned human repair genes fails to correct the repair defect in this cell strain. The defect in TTD1BR cells is therefore in a new gene involved in excision repair in human cells. The finding of a second dna repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |