RESUMO
Pertussis remains a public health concern in most countries. This cross-sectional study aims to investigate the distribution of pertussis toxin antibodies (anti-PT IgG) in Tunisian children and adolescents aged 3-18 years, to define optimal age for booster vaccination. Anti-PT IgG concentrations of enrolled participants were measured using commercial enzyme-linked immunosorbent assay. Concentrations were classified as: indicative of current/recent infection if ⩾100 IU/ml, indicative of recent exposure to Bordetella pertussis within the last year if 40-100 IU/ml and less likely revealing a recent exposure to B. pertussis if <40 IU/ml. Between March and June 2018, a total of 304 participants (mean age: 9.3 years) were included in this study. Overall, 12.8% (95% confidence interval (CI) 9.1%-16.6%) were seropositive (IgG levels ⩾40 IU/ml). Among them, 14.7% (95% CI 2.3%-23.3%) had levels indicative of a current/recent infection. The multivariate Poisson regression analysis suggested associations between female gender, as well as age group 13-18 years and 3-5 years and higher anti-PT IgG concentrations. Our results are consistent with the notion that vaccine-induced immunity decline, as well as circulation of pertussis among school children and adolescents enables them to be reservoirs of infection and disease transmission to vulnerable infants. Booster dose of acellular pertussis vaccine for school entrants is therefore recommended.
Assuntos
Anticorpos Antibacterianos/sangue , Antitoxinas/sangue , Toxina Pertussis/imunologia , Coqueluche/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Estudos Soroepidemiológicos , Tunísia/epidemiologiaRESUMO
Xeroderma pigmentosum (XP) is a form of general dermatosis characterised by photo-induced cutaneous-ocular impairment and by skin cancers. In addition to these signs, there may also be neurological involvement. This disease is related to a defect in genes within the nucleotide excision repair system for the first seven genetic groups (A-G), and to an abnormality in transcription groups for the eighth group (xeroderma pigmentosum variant - XPV). Cutaneous carcinomas are the most common types of cancer seen. They may begin in childhood. Multiple melanoma commonly occurs during the course of XP but given the frequency of spontaneous regression, the incidence is underestimated. The clinical appearance is characterised by polymorphous lesions with characteristic dyschromia and in most cases it is sufficient to establish the diagnosis. Investigation of unscheduled DNA synthesis (UDS) and cell survival following ultraviolet (UV) radiation were formerly considered the reference examination for laboratory diagnosis. However, these tests are now being replaced by new molecular biology techniques to screen for the genetic mutations characteristic of the disease. These techniques have proved extremely useful in identifying heterozygous patients and in antenatal diagnosis. Photoprotection is the key preventive measure: patients must avoid all exposure to the sun and to artificial sources of UV radiation. The therapeutic arsenal has recently been enriched by several modern therapeutic methods used to destroy cutaneous tumours such as imiquimod and photodynamic therapy (PDT). These approaches are valuable since they eliminate incipient tumours while sparing healthy skin. Surgery and cryosurgery are the most suitable methods for treating cutaneous tumours in children. Chemotherapy may be considered an alternative for the treatment of keratoacanthomas and squamous cell carcinomas (SCC). Cryosurgery may be combined with other therapeutic approaches to eliminate SCC of the lip. Management of these patients in reference centres, coupled with assistance from associations providing support for patients' families, has resulted in improved quality of therapy while slowing down disease progression.
Assuntos
Neoplasias Cutâneas , Xeroderma Pigmentoso , Neoplasias Oculares/etiologia , Predisposição Genética para Doença , Humanos , Neoplasias Induzidas por Radiação/genética , Neoplasias Induzidas por Radiação/terapia , Doenças do Sistema Nervoso/etiologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Xeroderma Pigmentoso/diagnóstico , Xeroderma Pigmentoso/genética , Xeroderma Pigmentoso/terapiaRESUMO
We use dispersive Fourier transformation to measure shot-to-shot spectral instabilities in femtosecond supercontinuum generation. We study both the onset phase of supercontinuum generation with distinct dispersive wave generation, as well as a highly-unstable supercontinuum regime spanning an octave in bandwidth. Wavelength correlation maps allow interactions between separated spectral components to be identified, even when such interactions are not apparent in shot-to-shot or average measurements. Experimental results are interpreted using numerical simulations. Our results show the clear advantages of dispersive Fourier transformation for studying spectral noise during supercontinuum generation.
Assuntos
Algoritmos , Iluminação/métodos , Modelos Teóricos , Razão Sinal-Ruído , Simulação por Computador , Sistemas Computacionais , Luz , Espalhamento de RadiaçãoRESUMO
Xeroderma pigmentosum (XP) is a rare genodermatosis predisposing to skin cancers. The disease is classified into eight groups. Among them, XP group A (XP-A) is characterized by the presence of neurological abnormalities in addition to cutaneous symptoms. In the present study, we report a particular family with XP-A in which some members showed an atypical clinical presentation, i.e. unexplained neurological abnormalities with discrete skin manifestations. Molecular investigation allowed identification of a novel XPA mutation and complete phenotype-genotype correlation for this new phenotypic expression of XP-A.
Assuntos
Doenças do Sistema Nervoso/genética , Proteína de Xeroderma Pigmentoso Grupo A/genética , Xeroderma Pigmentoso/genética , Adulto , Consanguinidade , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Doenças do Sistema Nervoso/metabolismo , Linhagem , Fenótipo , Tunísia , Xeroderma Pigmentoso/metabolismo , Proteína de Xeroderma Pigmentoso Grupo A/metabolismo , Adulto JovemRESUMO
BACKGROUND: Basal cell carcinoma (BCC) occurs frequently in young patients with xeroderma pigmentosum (XP). Because tumours are multiple and usually found on the face, alternatives to surgery are proposed. The purpose of this study was to evaluate the efficacy of cryosurgery for BCC in XP patients. PATIENTS AND METHODS: This was a retrospective study that included all instances of BCC occurring in XP patients treated by cryosurgery between January 2002 and October 2008. RESULTS: Forty-five cases of primary facial BCC and one case of relapsing BCC (16 on the cheeks, 11 on the nose, six on the face and five on the inner edge of the eye area) were treated by cryosurgery in 18 XP patients (average age: 18.7 years; sex ratio: 0.5). Mean carcinoma size was 10mm. Thirty-six tumours were nodular and 10 were nodular and ulcerated. Follow-up ranged from 16 to 60 months (mean: 30 months). Complications were rare. Cosmetic results were satisfactory. We noted 10 cases of hypopigmentation (21.7%) and one notch on the nose following treatment for recurrent BCC on a radiotherapy scar. Relapse occurred in one case (2.17%). CONCLUSION: Because of its simplicity, its good safety, its sparing of skin and its reliability of oncological outcome, cryosurgery is the treatment of choice for CBC in XP patients.
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Carcinoma Basocelular/cirurgia , Criocirurgia/métodos , Neoplasias Faciais/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Cutâneas/cirurgia , Xeroderma Pigmentoso/cirurgia , Adolescente , Adulto , Carcinoma Basocelular/diagnóstico , Criança , Neoplasias Faciais/diagnóstico , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Reoperação , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Xeroderma Pigmentoso/diagnóstico , Adulto JovemRESUMO
Xeroderma pigmentosum (XP, OMIM 278700-278780) is a group of autosomal recessive diseases characterized by hypersensitivity to UV rays. There are seven complementation groups of XP (XPA to XPG) and XPV. Among them, the XP group C (XP-C) is the most prevalent type in Western Europe and in the United States. We report here on the clinical and genetic investigation of XP-C patients in 14 Tunisian families. As the XPC V548A fs X572 mutation has been identified in Algerian and Moroccan populations, Tunisian patients were first screened for this mutation by a direct sequencing of exon 9 of the XPC gene. All patients with a severe clinical form had this mutation, thus showing the homogeneity of the mutational spectrum of XPC in Tunisia. A potential founder effect was searched and confirmed by haplotype analysis. Taking into account the similarity of the genetic background, we propose a direct screening of this mutation as a rapid and cost-effective tool for the diagnosis of XP-C in North Africa.
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Substituição de Aminoácidos/genética , Proteínas de Ligação a DNA/genética , Mutação da Fase de Leitura/genética , Xeroderma Pigmentoso/diagnóstico , Xeroderma Pigmentoso/genética , Adolescente , Adulto , Sequência de Bases , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Haplótipos , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Tunísia , Adulto JovemRESUMO
INTRODUCTION: Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by abnormal sensitivity to sunlight which results in pigmentary changes, telangiectases, keratoses and eventually carcinomata. Additional neurological complications can be associated. The aim of our study was to analyze particularities of neurological abnormalities of Tunisian patients. METHOD: We conducted a retrospective study in 62 patients suffering from XP included during the period 1992-2007. Patients were aged from 1 to 64 years (mean age: 17.6 +/- 11.4 years). Thirty patients were female and 32 were male. The patients had severe (n=16), variant (n=15) and moderate (n=31) XP. RESULTS: Neurological abnormalities were observed in 21 patients (33.9%). Mental retardation was observed in 15 of the 21 patients, pyramidal syndrome in five, cerebellar syndrome in two, extrapyramidal syndrome in two, microcephalia in two, choreoatetosis in three cases and a peripheral neuropathy in eight. No neurological disorder was observed in the XP-variant patients. Neurological abnormalities were more frequent in the patients with moderate XP (n=17, 64.5%) than with severe XP (p=0.051). CONCLUSION: This difference in a group of Tunisian patients confirms the heterogeneous nature of XP and is probably due to genetic heterogeneity.
Assuntos
Doenças do Sistema Nervoso/complicações , Xeroderma Pigmentoso/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Deficiência Intelectual/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tunísia , Adulto JovemRESUMO
We describe an experiment in which a train of femtosecond pulses is coupled into a photonic crystal fiber (PCF) by means of an offset pumping technique that can selectively excite either the mode LP(01) or LP(11) or LP(21). The PCF presents a wide range of wavelengths in which the fundamental mode experiences normal dispersion, whereas LP(11) and LP(21) propagate in the anomalous dispersion regime, generating a supercontinuum based on the soliton fission mechanism. We find that the existence of a cut-off wavelength for the higher-order modes makes the spectral broadening asymmetrical. This latter effect is particularly dramatic in the case of the LP(21) mode, in which, by using a pump wavelength slightly below cut-off, the spectral broadening occurs only on the blue side of the pump wavelength. Our experimental results are successfully compared to numerical solutions of the nonlinear Schrödinger equation.
Assuntos
Desenho Assistido por Computador , Cristalização/métodos , Tecnologia de Fibra Óptica/instrumentação , Iluminação/métodos , Modelos Teóricos , Simulação por Computador , Transferência de Energia , Desenho de Equipamento , Análise de Falha de Equipamento , Teoria QuânticaRESUMO
Mutations in the p53 gene were identified in five of eight non-melanoma skin tumors in the sun-exposed areas of xeroderma pigmentosum patients by the polymerase chain reaction and single strand conformation polymorphism analysis followed by sequencing of the DNA. All mutations occurred at the dipyrimidine sites, indicating that they were caused by UV irradiation. Two tumors had multiple mutations, and four tumors had nonsense mutations. Since xeroderma pigmentosum patients are extremely sensitive to UV, the solar UV should have caused the mutations in the p53 gene and the mutations must have played a significant role in UV tumorigenesis.
Assuntos
Carcinoma Basocelular/genética , Carcinoma de Células Escamosas/genética , Genes p53/genética , Genes p53/efeitos da radiação , Neoplasias Cutâneas/genética , Raios Ultravioleta/efeitos adversos , Xeroderma Pigmentoso/genética , Adolescente , Adulto , Sequência de Bases , Carcinoma Basocelular/complicações , Carcinoma de Células Escamosas/complicações , Criança , Códon/genética , Códon/efeitos da radiação , DNA de Neoplasias/genética , DNA de Neoplasias/efeitos da radiação , DNA de Cadeia Simples/análise , Éxons/genética , Éxons/efeitos da radiação , Humanos , Dados de Sequência Molecular , Mutação , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/genética , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/etiologia , Luz Solar/efeitos adversos , Xeroderma Pigmentoso/complicaçõesAssuntos
Carcinoma Basocelular/patologia , Neoplasias Cutâneas/patologia , Adulto , Feminino , HumanosRESUMO
Mutations in the p53 gene were analyzed in 23 squamous cell carcinomas (SCCs) and five basal cell carcinomas from 10 xeroderma pigmentosum patients in Tunisia. Fourteen mutations were detected. Most occurred at the dipyrimidine sequences of DNA, suggesting that they were caused by ultraviolet light. A strong correlation was noted between the presence of the p53 mutations and clinical characteristics such as histology and growth of SCC. In well-differentiated grade 1 SCCs, three (27.3%) of 11 tumors had the p53 gene mutations, whereas in grade 2 and grade 3 SCCs, six (85.7%) of seven tumors had the p53 gene mutations (p < 0.05). Tumors less than 8.0 mm in diameter showed a relatively low frequency of mutation (two of 10 tumors, 20.0%), whereas most of the tumors larger than 8.1 mm (seven of eight tumors, 87.5%) had mutations of the p53 gene (p < 0.025). Multiple tumors in the same xeroderma pigmentosum patients also showed this relation. These results suggest that mutations in the p53 gene lead to the invasive and rapid-growing character of SCC.
Assuntos
Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/genética , Genes p53 , Mutação , Neoplasias Cutâneas/genética , Xeroderma Pigmentoso/complicações , Adolescente , Adulto , Sequência de Bases , Carcinoma de Células Escamosas/patologia , Criança , Humanos , Sondas Moleculares/genética , Dados de Sequência Molecular , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologiaRESUMO
Trigeminal trophic syndrome, a rare cause of facial ulceration, is the consequence of damage to the trigeminal nerve or its central sensory connections. We report two cases of trigeminal trophic syndrome, complications of cerebral vascular accidents. A 65-year-old woman complained of numerous and progressive ulcers of the right side of her face of 2 month's duration. A 67-year-old woman presented with an ulcer of the ala nasi of 10 week's duration. This syndrome most commonly occurs in women with an average age of 57 years. About 100 cases are reported in the literature. The diagnosis is made on clinical grounds, and is suggested when loss of sensation occurs in association with unilateral facial ulceration, especially involving the ala nasi. Once the ulcers appear, they are extremely persistent.
Assuntos
Dermatoses Faciais/etiologia , Hipestesia/etiologia , Doenças Nasais/etiologia , Úlcera Cutânea/etiologia , Acidente Vascular Cerebral/complicações , Doenças do Nervo Trigêmeo/complicações , Idoso , Feminino , HumanosRESUMO
INTRODUCTION: Xeroderma pigmentosum is a relatively frequent genodermatosis in North Africa. It is characterized by abnormal sensitivity to ultraviolet light, responsible for the early occurrence of multiple cutaneous neoplasms. We present the results of the clinical and biological investigations in a family in which all its members exhibited xeroderma pigmentosum. PATIENTS AND METHODS: Since 1962, the father, mother, the 5 children and the maternal uncle were all followed-up in the dermatology department in Tunis for a variant of xeroderma pigmentosum. Clinical (dermatological, neurological and ophthalmologic), biological, photobiological and molecular biology investigations were carried out. RESULTS: Diagnosis of a variant of xeroderma pigmentosum was established on the delayed appearance (after the age of 4) of poikiloderma and the early onset of multiple carcinomas, without neurological disorders. Fifty-eight squamous cell and 3 basal cell carcinomas were diagnosed and treated by surgical exeresis or radiotherapy. The third child, treated with etretinate for 6 years, had developed 38 carcinomas. Contrary to the parents, whose first carcinomas had appeared at the age of 34 and 40 years, the cutaneous cancers in the children appeared early, between the ages of 17 and 24. The minimal erythematous dose was normal in all these patients. Conversely, the phototest revealed persistent erythema and the delayed appearance of multiple dyskeratosis cells. Molecular biology confirmed the diagnosis of xeroderma pigmentosum with the presence of a low level DNA repair. The third child, the father and the uncle respectively exhibited DNA repair rates of 32, 57 and 72%, compared with normal controls. The results of the complementarity tests conducted in the third child suggested that this family belonged to the genetic F group. Discussion The clinical and molecular data confirmed the diagnosis of xeroderma pigmentosum in this family and their genetic F group profile. However, this family exhibited clinical (the cutaneous involvement was more severe in the children) and molecular heterogeneity and the level of DNA repair was high in comparison with the levels (between 12 and 15%) reported by Japanese authors in group F xeroderma pigmentosum. The third child exhibited 10-fold more carcinomas that his siblings. This high rate of carcinoma may be explained by excessive exposure to sun and/or the retinoid treatment, particularly since his DNA repair rate (32%) was relatively high compared with that of severe (0-5%) and moderate (5-15%) forms of the disease.
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Xeroderma Pigmentoso/diagnóstico , Xeroderma Pigmentoso/genética , Seguimentos , Humanos , LinhagemRESUMO
INTRODUCTION: Despite prevention programs, tuberculosis is still progressing endemically in developing countries. The prevalence of cutaneous tuberculosis is estimated as 2.1 p. 100 and represents a rare localization among the extra-pulmonary forms. In order to study the epidemiology, the most frequent anatomoclinical forms and the progressive features of cutaneous tuberculosis, we conducted a study in the area of Tunis over a 20-year period. PATIENTS AND METHODS: All cases of cutaneous tuberculosis observed between 1981 and 2000 in the dermatology department of the Habib Thameur hospital were included in a retrospective study. Diagnosis of cutaneous tuberculosis was challenging and required the correlation of clinical, biological and progressive features. RESULTS: Twenty-six patients were observed in the study. There were 12 men and 14 women with a mean age of 30.4 years (range: 6-74) and 20 p. 100 of infantile cases. Of the various patterns of cutaneous tuberculosis seen, 11 (42 p. 100) had lupus tuberculosis, 10 (38 p. 100) had scrofuloderma, 4 (15 p. 100) had tuberculosis verrucosa cutis and 1 child had a perianal tubercular ulcer. The Mantoux test was positive in 20/24 patients. Histological tuberculoid granuloma was seen in 25 cases (96 p. 100) associated with caseating necrosis in 10 cases (38 p. 100). All patients were treated successfully with triple or quadruple anti-tubercular drugs for 6 to 10 months. One patient exhibited a squamous cell carcinoma on a lupus tuberculosis scar four years later. DISCUSSION: The progression of cutaneous tuberculosis remains stable, ranging from 1.4 cases/year between 1981 and 1990 to 1.2 cases/year between 1991 and 2000. In our study, females were slightly more affected than men with a M/F sex ration of 0.86. Before 1984, scrofuloderma was the most frequent form among the cutaneous tuberculoses. Now the frequency of lupus tuberculosis has reached that of scrofuloderma, demonstrating the increase in the incidence of clinical pattern of cutaneous tuberculosis with strong immunity probably related to the improvement in health conditions and generalization of vaccination programs.
Assuntos
Tuberculose Cutânea/patologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/epidemiologiaRESUMO
BACKGROUND: Xeroderma pigmentosum is a rare genodermatosis, with a defect affecting recovery of ultraviolet-induced damages and characterized by a high rate of malignancies of the exposed skin areas. We studied melanoma features of patients with xeroderma pigmentosum. PATIENTS AND METHODS: A retrospective study of xeroderma pigmentosum patients admitted to the Charles Nicolle Hospital of Tunis between 1973 and 1998. RESULTS: Two hundred sixteen patients with xeroderma pigmentosum were registered. Melanoma was present in 12 patients, 7 females and 5 males. Two patients were sisters. Cutaneous melanoma was found in 8 patients. Four patients presented with metastatic melanoma. The median age for development of the first melanoma was 17.5 years. All of the cutaneous melanomas were found on the face. Lentigo malignant melanoma was reported in 3 cases. The tumors were treated with surgical excision. Except for a melanoma affecting the orbit, characterized by a fatal outcome, no metastases were detected at the different investigations. DISCUSSION: Melanoma occurs frequently in patients with xeroderma pigmentosum, it has been reported in 5.5 p. 100 of cases and 11.3 p. 100 of patients with cutaneous carcinoma. The age of onset was low: 17.5 years. It appeared later than the carcinoma. The location of cutaneous melanoma in face in xeroderma pigmentosum patients indicates that they were caused mainly by sunlight exposure. Lentigo malignant melanoma was the most frequent type. Prognosis is difficult to define owing to the large number of other cutaneous malignancies. Apart from one case of rapidly fatal orbital melanoma, we recorded long survivals even in cases of melanoma revealed by metastases.
Assuntos
Melanoma/etiologia , Neoplasias Orbitárias/etiologia , Neoplasias Cutâneas/etiologia , Xeroderma Pigmentoso/complicações , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Hospitalização/tendências , Humanos , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Melanoma/cirurgia , Neoplasias Orbitárias/epidemiologia , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Luz Solar/efeitos adversos , Análise de Sobrevida , Tunísia/epidemiologia , Xeroderma Pigmentoso/genéticaRESUMO
The incidence of condylomata acuminata is increasing in all countries. They are one of the most frequent sexually transmitted disease (STD). The authors reported the experience of the department of Dermatology of charles Nicolle's hospital between the year 1979 and 1998. This HPV infections were in the third position of the STD and occurred mainly in young males. The clinical lesions are genital condylomata. They were successfully treated with electrodessication or cryotherapy.
Assuntos
Condiloma Acuminado/epidemiologia , Adulto , Condiloma Acuminado/patologia , Condiloma Acuminado/terapia , Crioterapia , Dessecação , Feminino , Humanos , Incidência , MasculinoRESUMO
UNLABELLED: Human papillomavirus (HPV) infection tend to be the most prevalent sexually transmitted disease (STD), and "high-risk" HPV types are correlated to intra-epithelial neoplasia, especially cervical cancer. The aim of this study was to evaluate the frequency of "high risk" HPV types in condyloma. PATIENTS AND METHODS: A non randomised prospective study was performed, including 24 patients with condyloma examined in the department of Dermatology of Charles Nicolle's hospital. Molecular hybridisation method was realised for all patients to identify HPV type. RESULTS: Mean age of the 24 patients was 37.8 years Ratio (male/female): 1.4 In 21 patients HPV DNA was detected 2 women had "high risk" HPV type (9.5%).
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Condiloma Acuminado/epidemiologia , Condiloma Acuminado/virologia , Papillomaviridae/classificação , Adulto , Distribuição por Idade , Condiloma Acuminado/complicações , Feminino , Humanos , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Tunísia/epidemiologia , Neoplasias do Colo do Útero/virologiaRESUMO
AIMS: Xeroderma pigmentosum (XP, OMIM 278700-278780) is one of the most severe genodermatoses and is relatively frequent in Tunisia. In the absence of any therapy and to better manage the disease, we aimed to develop a molecular tool for DNA-based prenatal diagnosis. METHODS: Six consanguineous Tunisian XP families (4 XP-A and 2 XP-C) have benefited from a prenatal diagnosis. Screening for mutations was performed by direct sequencing, while maternal-foetal contamination was checked by genotyping. RESULTS: Among the 7 prenatal diagnoses, 4 foetuses were heterozygous for the screened mutation. Exclusion of contamination by maternal cells was checked. Mutations were detected at a homozygous state in the remaining cases, and the parents decided to terminate pregnancy. CONCLUSION: Our study illustrates the implementation of prenatal diagnosis for better health support of XP in Tunisia.
Assuntos
Diagnóstico Pré-Natal , Encaminhamento e Consulta , Xeroderma Pigmentoso/diagnóstico , Aborto Eugênico , Adulto , Consanguinidade , Análise Mutacional de DNA , Feminino , Heterozigoto , Homozigoto , Humanos , Mutação/genética , Gravidez , Tunísia , Xeroderma Pigmentoso/genéticaRESUMO
Xeroderma pigmentosum (XP) is a rare disorder characterized by a high skin sun-sensitivity predisposing to skin cancers at an early age. Among Tunisian XP patients with an intermediate skin phenotype, 92% presented neurological abnormalities related to XPA gene deficiency. Clinical variability of the XP-A phenotype is associated with a mutational heterogeneity. In the present study, two Tunisian families with severe dermatological and neurological XP phenotypes were investigated in order to determine clinical characteristics and genetic basis. Two Tunisian families with four XP affected children were examined in the Dermatology Department. Clinical features showed severe presentation of the disease. Coding regions of the XPA gene were analysed by direct sequencing. Results showed the presence of a novel mutation, p.E111X, in three patients belonging to the same family and presenting a very severe phenotype i.e. development of skin lesions and neurological signs before 1 year age. For the other patient, we identified a nonsense mutation, p.R207X, already identified in a Palestinian XP-A patient. Identification of novel causing mutations in Tunisian XP-A patients shows the genetic and mutational heterogeneity of the disease in Tunisia. Despite a relatively homogenous mutational spectrum, mutational heterogeneity for rare cases is observed because of the high rate of consanguinity.