Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0349506 (photosensitivity)
 4,145 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-six patients with xeroderma pigmentosum (XP), who live in the Northeast (Tohoku) District of Japan, were examined for the clinical characteristics of UV-induced DNA synthesis (unscheduled DNA synthesis, UDS) and UV sensitivity of skin fibroblasts or lymphoblastoid cells, or both. A history of consanguineous marriage within two generations was found in 19 of 26 cases (73%). Two pairs of siblings showed similar manifestations and almost the same levels of UDS and of UV sensitivity. Squamous cell carcinoma, basal cell carcinoma, or both were observed on the exposed skin in 14 patients, but no malignant melanoma was found. Cancer had developed in approximately 71% (10/14) of the cancer-bearing patients by the age of 20, and 8 of them belonged to the UDS-deficient group. Neurological manifestations were associated with nine patients, including 3 with typical de Sanctis-Cacchione syndrome (DSC), and most of the cells derived from these patients had a UDS level less than 10% of that of the normal cells. A clear correlation between the levels of UDS and UV sensitivity, on the one hand, and the severity of clinical manifestations on the other could not be detected, but it seems that the UDS-deficient group is generally much more sensitive to UV in terms of cell killing and the induction of sister chromatid exchange (SCE) than the UDS-proficient group. After a photosensitivity test, one patient with mild skin manifestations showed distinct skin tanning without preceding erythema.
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PMID:Clinical and biological studies of 26 cases of xeroderma pigmentosum in northeast district of Japan. 397 May 83

There are multiple genetic disorders with photosensitivity. The first large group consists of the porphyrias about which a great amount of knowledge has accumulated. The second group is not as well-defined for they are the heredodegenerative disorders of which xeroderma pigmentosum is the most important because here the basic defect in DNA repair is known. Some of the aminoacidurias may cause photosensitivity because of pigment dilution or pellagra-like states. The last group consisting of Darier's, polymorphic light eruption and others are poorly understood, and photosensitivity here is not present in all cases.
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PMID:The genetics of the photodermatoses. 495 Sep 28

Out of a total of 370 patients with photosensitivity disorders, the light sensitivity had started at an age of 15 years or earlier in 95 cases (26%). Seventy-eight of these suffered from polymorphous light eruptions (PMLE). In half of the PMLE cases the morphology of the light-induced rash was classified as prurigo-like, and in one-fourth as vesicopapular. Other registered photodermatoses with childhood onset were xeroderma pigmentosum, erythropoietic protoporphyria, systemic lupus erythematosus and pellagra. No childhood cases of photosensitivity from external chemicals or internal medication were encountered.
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PMID:Photosensitivity in childhood. 695 15

Instrumentation for studying action spectra in controls and various light-associated diseases is described. This study summarizes tests performed with a prism grating monochromator during the last 10 yr. There were 68 photodermatoses studied: xeroderma pigmentosum (XP) (1), lupus erythematosus (LE) (12), polymorphous light eruption (PLE) (23), solar urticaria (4), actinic reticuloid (2), halogenated salicylanilide photosensitivity and persistent light reactors (11), psoralen photosensitivity (6), and porphyria (9). A normal minimal erythema dose in the UVB (below 320 nm) was generally observed in polymorphous light eruption and lupus erythematosus. The most exquisite photosensitivity for delayed erythema was observed in actinic reticuloid, which in one case was 25-35 times more sensitive in the UVB range which was also observed but to a lesser extent in XP and in persistent light reactors. Persistence of erythema and edema at test sites was observed in XP, PLE, LE, and actinic reticuloid. A delay in development of erythema reaching a maximum at 72 hr was observed in XP and psoralen phototoxicity. Maximum photosensitivity occurred in solar urticaria. Three patients had peak sensitivity in the range of 310-313 nm and the 4th at 460 nm. Photosensitivity in the visible range was detected in 2 patients with solar urticaria, one with actinic reticuloid, and confirmed in 9 patients with porphyria (405 nm). Photosensitivity in the UVA (above 320 nm) occurred to some degree in all groups.
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PMID:Instrumentation and action spectra in light-associated diseases. 725 55

In several patients with the rare hereditary disorder trichothiodystrophy (TTD), a DNA repair defect has been shown to be in the same gene as in xeroderma pigmentosum complementation group D (XP-D). The ERCC-2 gene (excision repair cross-complementing rodent repair deficiency of group 2) has recently been identified as a strong candidate gene for XP-D, since it restores normal UV sensitivity to XP-D cells after transfection. Using Southern blotting, we have analysed the ERCC-2 gene in DNA samples from 28 members of nine Italian families with individuals affected by XP-D (three patients) or by TTD with photosensitivity due to the XP-D defect (eight patients). No major modifications of the ERCC-2 gene were detected with two cDNA probes in either XP-D or TTD patients indicating that the association between TTD and XP-D is not likely to result from a large deletion or rearrangement involving this gene. We found two RFLPs after digestion of the DNA samples with TaqI or MspI, but neither of them could be related to the molecular alteration determining the pathological phenotype. We also analysed a human homologue detected with the hamster sequence isolated by Arrand et al. (1989), which specifically, but partially, complements the DNA repair deficiency in XP-D cells. Our analysis demonstrated that this gene is not the primary gene defective in XP-D. In fact two RFLPs detected with a genomic probe do not co-segregate with the disease in an XP-D family.
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PMID:Molecular analysis of the XP-D gene in Italian families with patients affected by trichothiodystrophy and xeroderma pigmentosum group D. 751 Mar 65

We report an 18-year-old Japanese woman who had mild photosensitivity and a facial tumour, which was shown to be a morphoeic basal cell carcinoma. Although a line of fibroblasts derived from the patient, Kps6 cells, were slightly more sensitive to UV irradiation than normal cells, their level of unscheduled DNA synthesis was about 20% that of normal cells, and recovery of RNA synthesis after UV irradiation was moderately depressed. Complementation tests, carried out by cell fusion or by microinjection of plasmids harbouring xeroderma pigmentosum (XP) genes, indicated that the patient had XP group F. To our knowledge, this is the youngest XP group F patient with a malignant tumour reported to date.
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PMID:A young woman with xeroderma pigmentosum complementation group F and a morphoeic basal cell carcinoma. 775 23

We describe a girl with photosensitivity (P), ichthyosis (I), brittle hair (B), impaired intelligence (I), possibly decreased fertility (D), and short stature (S). The clinical findings fit into the PIBI(D)S syndrome and trichothiodystrophy. A remarkable and probably unique observation for this disorder was the intermittent character of the scalp hair loss during infectious periods in this patient. Easy suntanning suggested photosensitivity and prompted DNA repair studies which demonstrated reduced UV-induced DNA repair synthesis. Subsequent studies have assigned this patient to xeroderma pigmentosum group D and suggested a specific deficiency of 6-4 photoproduct repair. An unaffected child was diagnosed in the next pregnancy of the mother.
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PMID:Intermittent hair loss in a child with PIBI(D)S syndrome and trichothiodystrophy with defective DNA repair-xeroderma pigmentosum group D. 780 14

The mechanisms mediating the varied effects of ultraviolet radiation (UVR) on human skin are unclear, although a relationship between erythema and DNA damage is suggested by photosensitivity in xeroderma pigmentosum. Increased p53 expression in response to UVR is thought to reflect direct DNA damage, but recent evidence indicates that UVR also activates membrane and cytosolic signal transduction pathways. In this study, we have investigated the relationship between erythema and p53 induction following UVB and whether this p53 response is specific to UVR. p53 protein expression was determined by immunocytochemistry using the monoclonal antibody DO7, and p53 mRNA expression was examined by non-isotopic in situ hybridization. Incremental doses of UVB were administered to the lower back of eight subjects. Immunostaining revealed that p53 positive nuclei were significantly increased 8 h after suberythemogenic doses of UVB (79 +/- 12), compared to normal unirradiated skin (8 +/- 6, p < 0.0005), but no change in p53 mRNA was seen. Higher UVB doses, which resulted in moderate erythema, resulted in a similar or greater induction of p53 protein. Indomethacin (1% w/v), applied immediately after UVB irradiation, significantly inhibited UVB erythema at 8 h in six subjects (p < 0.005), but did not reduce p53 immunostaining. Dithranol (1 microgram/microliter, n = 8), sodium dodecylsulphate (5%, n = 4), and retinoic acid (0.5%, n = 4), applied for 48 h, caused erythema, significantly increased p53 protein levels (p < 0.05), and also increased p53 mRNA. Our results show that in human skin, UVB-induced p53 elevation can be dissociated from erythema and skin irritants can also induce p53 protein. The induction of p53 mRNA by irritants but not UVR suggests different mechanisms of action.
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PMID:Dissociation of erythema and p53 protein expression in human skin following UVB irradiation, and induction of p53 protein and mRNA following application of skin irritants. 793 Jun 73

Trichothiodystrophy (TTD), an autosomal recessive disorder characterized by sulfur-deficient brittle hair, identifies a group of genetic disorders with an altered synthesis of high-sulfur matrix proteins and a defect in excision repair of ultraviolet damage in fibroblasts of most TTD patients. In contrast to patients with xeroderma pigmentosum (XP), TTD patients do not have an increased frequency of skin cancers. TTD patients may be grouped into four categories: 1) those without photosensitivity and without a defect in excision repair of UV damage; 2) those without photosensitivity and with an excision-repair defect in the same gene as in XP-D (complementation group D); 3) those with photosensitivity and with the XP-D repair defect; 4) those with photosensitivity and with a repair defect distinct from that in XP-D. We present a brother and sister in the third category of TTD. Clinically, the patients have brittle hair, short stature, ichthyosis, photosensitivity, nail and dental dysplasias, cataracts, mental retardation, and pyramidal tract abnormalities. Diagnosis was made by hair mount, which shows the characteristic banding pattern with polarizing microscopy, and by hair amino acid analysis, which demonstrated decreased high-sulfur matrix proteins. Fibroblasts cultured from skin biopsies had a marked DNA excision repair defect similar to the repair defect seen in XP-D. We have documented a unique dysmyelinating disorder on magnetic resonance imaging of the brain that might explain their mental retardation, marked hyperactivity, and neurologic deficits. Following the discovery that the human excision repair cross complementing rodent ultraviolet group 2 (ERCC2) gene is able to correct the ultraviolet sensitivity of XP-D cell strains, the ERCC2 cDNA from previous TTD patients was sequenced and shows frameshifts, deletions and point mutations in the ERCC2 gene. Molecular analysis of our patients is in progress. Molecular analysis of the defects in ERCC2 in clinically distinct patients with XP,XP/Cockayne's syndrome, and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders.
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PMID:Trichothiodystrophy: clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings. 796 80

Trichothiodystrophy (TTD) is a rare autosomal recessive disease characterized by brittle hair with reduced sulfur content, mental and physical retardation, a peculiar face and ichthyosis. Photosensitivity has been reported in approximately 20% of the cases in the literature. DNA repair investigations demonstrated that clinical photosensitivity is usually associated with an enhancement of the cellular UV-sensitivity and that the repair defect is in the same gene as in patients from group D of xeroderma pigmentosum (XP). In this paper we describe the characterization of 13 further TTD patients; a defect in the nucleotide-excision repair was observed in fibroblast strains from 10 patients, confirming that TTD is frequently associated with DNA repair defects. Genetic analysis based on complementation studies demonstrated the presence of the XP-D defect in seven repair-defective TTD cases, indicating definitively that the concurrence of TTD with XP-D is not a sporadic or casual event. However, three further cell strains (TTD4VI and TTD6VI from two French siblings and TTD1BR from an English patient) showed restoration of normal UV-induced DNA repair synthesis after fusion with XP or TTD cells belonging to XP group D. These observations, which give the first indication that TTD is associated with repair defects behaving differently in the functional test of complementation, suggest some kind of causal connection between defective excision-repair factors and clinical features diagnostic for TTD. A peculiar aspect of TTD in which repair deficiencies are not related to an increased susceptibility to cancer is confirmed also in all the repair-defective TTD patients investigated in this paper.
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PMID:Genetic heterogeneity of the excision repair defect associated with trichothiodystrophy. 850 95


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