RESUMO
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.
Assuntos
Mutação/genética , Proteína de Xeroderma Pigmentoso Grupo A/metabolismo , Xeroderma Pigmentoso/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Progressão da Doença , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Linhagem , Fenótipo , Polimorfismo Genético , Tunísia , Xeroderma Pigmentoso/fisiopatologia , Proteína de Xeroderma Pigmentoso Grupo A/genéticaRESUMO
We report the identification of two novel polymorphisms in the PRKAG2 gene and preliminary association study between 5'-UTR and exon 1 polymorphisms with susceptibility to type 2 diabetes. No association with type 2 diabetes was identified. However, one of these newly identified polymorphisms (p.Ser20Ile) is likely associated with cardiac disease.
Assuntos
Proteínas Quinases Ativadas por AMP/genética , Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Éxons/genética , Variação Genética , Polimorfismo de Nucleotídeo Único , Regiões 5' não Traduzidas/genética , Idade de Início , Idoso , Sequência de Bases , Diabetes Mellitus Tipo 2/complicações , Humanos , Anamnese , Pessoa de Meia-Idade , Dados de Sequência Molecular , Valores de Referência , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , TunísiaRESUMO
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.
