Asunto(s)
Xerodermia Pigmentosa/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias/genética , Neoplasias/mortalidad , Linaje , Túnez/epidemiología , Xerodermia Pigmentosa/mortalidad , Adulto JovenRESUMEN
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.
Asunto(s)
Diagnóstico Prenatal , Derivación y Consulta , Xerodermia Pigmentosa/diagnóstico , Aborto Eugénico , Adulto , Consanguinidad , Análisis Mutacional de ADN , Femenino , Heterocigoto , Homocigoto , Humanos , Mutación/genética , Embarazo , Túnez , Xerodermia Pigmentosa/genéticaRESUMEN
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.
Asunto(s)
Enfermedades del Sistema Nervioso/genética , Proteína de la Xerodermia Pigmentosa del Grupo A/genética , Xerodermia Pigmentosa/genética , Adulto , Consanguinidad , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Enfermedades del Sistema Nervioso/metabolismo , Linaje , Fenotipo , Túnez , Xerodermia Pigmentosa/metabolismo , Proteína de la Xerodermia Pigmentosa del Grupo A/metabolismo , Adulto JovenRESUMEN
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.