Case Of Xeroderma Pigmentosum Research Articles

Analysis of Mutations in the XPD Gene in Italian Patients with Trichothiodystrophy: Site of Mutation Correlates with Repair Deficiency, but Gene Dosage Appears to Determine Clinical Severity

Xeroderma pigmentosum (XP) complementation group D is a heterogeneous group, containing patients with XP alone, rare cases with both XP and Cockayne syndrome, and patients with trichothiodystrophy (TTD). TTD is a rare autosomal recessive multisystem disorder associated, in many patients, with a defect in nucleotide-excision repair; but in contrast to XP patients, TTD patients are not cancer prone. In most of the repair-deficient TTD patients, the defect has been assigned to the XPD gene. The XPD gene product is a subunit of transcription factor TFIIH, which is involved in both DNA repair and transcription. We have determined the mutations and the pattern of inheritance of the XPD alleles in the 11 cases identified in Italy so far, in which the hair abnormalities diagnostic for TTD are associated with different disease severity but similar cellular photosensitivity. We have identified eight causative mutations, of which four have not been described before, either in TTD or XP cases, supporting the hypothesis that the mutations responsible for TTD are different from those found in other pathological phenotypes. Arg112his was the most common alteration in the Italian patients, of whom five were homozygotes and two were heterozygotes, for this mutation. The presence of a specifically mutated XPD allele, irrespective of its homozygous, hemizygous, or heterozygous condition, was always associated with the same degree of cellular UV hypersensitivity. Surprisingly, however, the severity of the clinical symptoms did not correlate with the magnitude of the DNA-repair defect. The most severe clinical features were found in patients who appear to be functionally hemizygous for the mutated allele.

Spontaneous Corneal Scarring in Xeroderma Pigmentosum

The main purpose of this report is to describe nine cases of xeroderma pigmentosum with primary spontaneous corneal scarring in the absence of history of corneal ulcers or infectious keratitis. The authors studied nine patients with xeroderma pigmentosum. Each patient underwent complete ophthalmologic and dermatologic examinations. Three patients underwent excision of squamous cell carcinoma of the conjunctiva. There were five male and four female patients, with a mean age of 14 years and a range of 5 to 21 years. Seven had conjunctival squamous cell carcinoma. All patients had spontaneous diffuse corneal stromal scars without clinical evidence of keratitis and no previous history of corneal ulcer. The corneal sensation was intact. None of the patient had ulceration of the cornea. One patient had dry eye syndrome. The clinical and histopathologic changes of the cornea and conjunctiva in patients with xeroderma pigmentosum appear to be similar to the changes occurring in sun-exposed skin. This suggests that direct exposure of corneal and conjunctival tissue to ultraviolet light in patients with xeroderma pigmentosum is the primary cause of scarring in the cornea and conjunctiva, which leads to loss of vision.

A Case of Xeroderma Pigmentosum Associated with Squamous Cell Carcinoma

Xeroderma pigmentosum is a rare autosomal recessive disorder characterized by extreme photosensitivity and defect in repair of damage to DNA Lentigenes, freckles, telangiectasia and the hyperpigmented cutaneous macules in the sun-exposed area and early development of cutaneous malignancies are observed. In addition to cutaneous symptoms, ophthalmologic changes and neurologic abnormalities can be associated. We report a case of xeroderma pigmentosum associated with squamous cell carcinoma in a 4-year-old girl. This case is thought to be more earlier development of malignancies than ever reported.

Facial Resurfacing in Xeroderma Pigmentosum with Monoblock Full-Thickness Skin Graft

A case of xeroderma pigmentosum with multiple skin tumors on the face that was treated with total excision and replacement of face skin except the eyelids with a monoblock full-thickness abdominal skin graft is reported. The quality and tumor-free features of the monoblock full-thickness skin graft in xeroderma pigmentosum are indicated. Despite the increased morbidity of the donor region, the radical surgical approach advocated here has improved the prognosis in the case reported.

Xeroderma pigmentosum (3 observations)

Three cases of Xeroderma pigmentosum are reported, one of whom developed skin carcinogenesis before the age of 3. Defective DNA repair causes skin cancer and neurodegeneration. Management of such patients include the use of topical and systemic photoprotective drugs together with oral administration of retinoids for epithelioma prevention. Antenatal diagnosis by amniocentesis is possible.

Xeroderma pigmentosum : A giant malignant melanoma

A case of xeroderma pigmentosum (XP) with a giant malignant melanoma of the lower lip in a 14-year-old male is reported. The tumor was excised. The patient has a three year follow-up and has no local recurrence or metastasis.

Facial resurfacing in xeroderma pigmentosum: are we spoiling the ship for a ha'p'orth of tar?

A case of xeroderma pigmentosum (XP) is reported whose treatment included sub-total excision of facial skin and resurfacing in aesthetic units with grafts of relatively undamaged buttock skin. The principle of resurfacing is logical and supported by this and other reports which are reviewed. Though control was achieved in the grafted areas, tumours continued to develop in adjacent ungrafted skin. The importance of radical excision of exposed skin in severe cases of XP is emphasised.

A Case of Xeroderma Pigmentosum Group F With Late Onset of Clinical Symptoms

<h3>To the Editor.—</h3> Xeroderma pigmentosum (XP) is a genetic disease characterized by photosensitivity and early appearance of skin cancers. To date, nine genetic complementation groups from A to I have been identified.^1-3The complementation group F was first reported by Arase et al in 1979,⁴and three more cases have been identified in Japan.¹Its characteristic features are mild clinical manifestations and late onset, despite apparently low DNA repair capacities in the cells cultured from the patients. In this letter, we describe another case of XP F that developed in a 49-year-old woman, who had not noticed photosensitivity until she was examined. <h3>Report of a Case.—</h3> A 49-year-old woman was sent to the outpatient clinic of the dermatology department by her family physician because of a generalized eruption. Amoxicillin trihydrate was administered in August 1981 for a suppurating brown nodule, measuring 0.8 × 0.6 cm on the

Carcinoma of the tongue in a patient with xeroderma pigmentosum

A case of xeroderma pigmentosum with squamous cell carcinoma of the tongue is reported and the literature is briefly reviewed. The case not only confirmed all previously reported findings on the inherited disorder, but also presented further evidence that even regions not exposed to sunlight may be vulnerable to carcinomatous transformation in xeroderma pigmentosum.

Fetal case of xeroderma pigmentosum--first report of an autopsy case.

Fetal autopsy case of xeroderma pigmentosum was reported. This male fetus of 24 gestational weeks was prenatally diagnosed as xeroderma pigmentosum by detecting the DNA-repair defect of the amniotic fluid cells. Autopsy revealed not only maldevelopment of the fetus (stillbirth) in general for the standard, but also showed slight developmental retardation of various organs including kidneys and lungs, which could be examined by microscopic analysis. It was suggested that abnormality of the somatic organs began to appear at the fetal stage in this case of xeroderma pigmentosum.

Levels of DNA polymerases α and β in fibroblasts from different cases of Xeroderma pigmentosum: U. Bertazzoni, M. Stefanini, G. Pedrali-Noy, F. Nuzzo and A. Falaschi, Laboratorio di Genetica Biochimica ed Evoluzionistica del Consiglio Nazionale delle Ricerche, 27100 Pavia (Italia)

Levels of DNA polymerases α and β in fibroblasts from different cases of Xeroderma pigmentosum: U. Bertazzoni, M. Stefanini, G. Pedrali-Noy, F. Nuzzo and A. Falaschi, Laboratorio di Genetica Biochimica ed Evoluzionistica del Consiglio Nazionale delle Ricerche, 27100 Pavia (Italia)

Xeroderma pigmentosum and band-shaped nodular corneal dystrophy.

A case of xeroderma pigmentosum with associated band-shaped nodular dystrophy of the cornea is discussed. Band-shapped nodular dystrophy of the cornea usually occurs in elderly Bantu men. Band-shaped nodular dystrophy in a young Bantu man suffering from a genetically determined solar sensitive disease lends credence to the possibility that band-shaped nodular dystrophy is a solar sensitive disease, as has so often been postulated.

Levels of DNA polymerase-alpha and beta in normal and xeroderma pigmentosum fibroblasts.

We have determined the levels of DNA-polymerases-alpha and-beta in fibroblasts obtained from normal subjects and from patients with Xeroderma Pigmentosum (XP) belonging to three different complementation groups and to the variant form. The assays have been performed in crude extracts and after fractionation on sucrose gradients. The levels of alpha and beta-polymerases in the different cases of XP were found to lie within the same range as the control values, and no correlation was found with the severity of the symptoms. The sedimentation coefficients of the two polymerases from all the pathological lines were identical to those of the normal fibroblasts.

The Genetic Defect in the De Sanctis-Cacchione Syndrome

A family with five children affected with the de Sanctis-Cacchione (DSC) syndrome is presented. Ultraviolet light-induced DNA repair synthesis, as measured by autoradiography as well as by isopyknic centrifugation was studied in cell strains from three affected members and their heterozygote parents. Similar, low amounts of repair synthesis were found in the cells of all patients. In cell strains from the heterozygous parents a reduced repair activity was demonstrated. Complementation studies with cell hybridization techniques were performed using cells of our patients, cells of one of our patients and those of an unrelated DSC patient, and cells of one of our patients and those of a classic xeroderma pigmentosum (XP) patient. The fusion of cells front a classic XP patient with those ot one of our DSC patients resulted in hybrids that had nomal amounts of repair synthesis. The hybrids resulting from the other fusions revealed very low or negligible repair activity. These results demonstrate genetics heterogeneity between DSC and classical XP cases. They strongly suggest either intergenic or interallelic complementation during hybridization between XP and DSC cells.

Report of a case of xeroderma pigmentosum.

SUMMARY A case of xeroderma pigmentosum of late onset is reported in a boy who later developed a teratoma of the testis.

Muscular abnormality in xeroderma pigmentosum: High resolution light-microscopy and electron-microscopic observations

Two cases of xeroderma pigmentosum and 1 case of the De Sanctis-Cacchione syndrome are presented. Muscle biopsies from all 3 patients showed identical alterations in 1 μ and 600 Å thin sections. The alterations consisted of massive accumulation of glycogen and subsarcolemmal mitochondrial aggregates. No similar lesion in muscle from xeroderma pigmentosum or the De Sanctis-Cacchione syndrome has been reported. A common aetiological mechanism is postulated for the muscle and skin lesions.

Xeroderma Pigmentosum.

Five cases of xeroderma pigmentosum have been presented, three of the patients belonging to one family. There was no history of consanguineous marriages in this series. All five patients had advanced ocular complications. Three presented with multiple basal cell carcinomata, which were treated by radiotherapy in two cases and surgery in one. One patient presented with a dermatofibroma, which does not seem to have been reported earlier in association with this disease. Reconstructive techniques such as the use of flaps and grafts arc safe, and the healing response is quite satisfactory.

先天異常性皮膚疾患の成因に関する研究

In order to investigate a genetic aspect of congenital functional and/or biochemical anomalies of the skin, chromosome analysis of cells cultured from the leucocyte component of the blood obtained from six cases of keratosis palmaris et plantaris hereditarium, nine of ichthyosis vulgaris, two of keratosis follicularis, two of Darier’s disease, one of dyschromatosis symmetrica hereditaria, two of xeroderma pigmentosum and six of atopic dermatitis were performed, revealing following results. 1) Long Y chromosome was found in one case of ichthyosis vulgaris. 2) One case of keratosis palmaris et plantaris hereditarium showed low modal cell percentage, compared with control, which was statistically significant (p>0.05). 3) In one case of keratosis palmaris hereditarium and one of xeroderma pigmentosum, the rates of appearance of hyperdiploid cells were significantly higher than in control (p<0.05). 4) In one case of xeroderma pigmentosum and two of atopic dermatitis, the occurence of breaks was more frequent than in control, which was statistically significant (p<0.05). 5) Aneuploid cells and structual abnormalities of chromosomes showed a tendancy to appere more frequently in the group of functional and/or biochemical anomalies, such as keratosis follicularis, Darier’s disease, dyschromatosis symmetrica hereditaria, xeroderma pigmentosum and atopic dermatitis than in the group of organic anomalies such as phacomatosis and nevus described in the 1st report.

Ultrastructural changes in the epidermis of Xeroderma pigmentosum lesions in various stages of development.

The remarkable findings from an ultrastructural study of desquamating and dyskeratotic lesions of 4 cases of Xeroderma Pigmentosum are:

Investigations on dark repair in various light sensitive inherited disorders.

Defective dark repair is confirmed in 3 cases of Xeroderma pigmentosum while in one case of Bloom-syndrom and in 4 other light sensitive inherited disorders the mentioned enzyme system seems to be functional.