RESUMO
The nature and frequency of the major CFTR mutations in the North African population remain unclear, although a small number of CFTR mutation detection studies have been done in Algeria and Tunisia, showing largely European mutations such as F508del, G542X and N1303K, albeit at different frequencies, which presumably emerged via population admixture with Caucasians. Some unique mutations were identified in these populations. This is the first study that includes a genetic and clinical evaluation of CF patients living in Algeria. In order to offer an effective diagnostic service and to make accurate risk estimates, we decided to identify the CFTR mutations in 81 Algerian patients. We carried out D-HPLC, chemical-clamp denaturing gradient gel electrophoresis, multiplex amplification analysis of the CFTR gene and automated direct DNA sequencing. We identified 15 different mutations which account for 58.5% of the CF chromosomes. We used a quantitative PCR technique (quantitative multiplex PCR short fragment fluorescence analysis) to screen for deletion/duplication in the 27 exons of the gene. Taking advantage of the homogeneity of the sample, we report clinical features of homozygous CF patients. As CFTR mutations have been detected in males with infertility, 46 unrelated Algerian individuals with obstructive azoospermia were also investigated.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Argélia/epidemiologia , Azoospermia/genética , Criança , Pré-Escolar , Fibrose Cística/epidemiologia , Análise Mutacional de DNA , Feminino , Humanos , MasculinoRESUMO
The spectrum of cystic fibrosis (CF) mutations in the North African population remains poorly known. In order to offer an effective diagnostic service and to determine accurate risk estimates, we decided to identify the CF mutations in 10 Algerian CF families. We carried out a chemical-clamp denaturing gradient gel electrophoresis analysis of the CFTR gene and automated direct DNA sequencing. We identified 5 mutations and we characterized 60% of the CF chromosomes. Taking advantage of the homogeneity of the sample, we report clinical features of homozygous CF patients.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Argélia , Criança , Pré-Escolar , Éxons , Feminino , Deleção de Genes , Humanos , Íntrons , Masculino , Mutação , Mutação Puntual , Análise de Sequência de DNAAssuntos
Fibrose Cística/genética , Proteínas de Membrana/genética , Argélia , Alelos , Sequência de Bases , Regulador de Condutância Transmembrana em Fibrose Cística , DNA/genética , Mutação da Fase de Leitura , Humanos , Dados de Sequência Molecular , Família Multigênica , Ácidos Nucleicos Heteroduplexes/genética , Polimorfismo Genético , Sequências Repetitivas de Ácido NucleicoRESUMO
When screening for the presence of major cystic fibrosis mutations in Algerian cystic fibrosis families by heteroduplex formation, aberrant heteroduplexes were observed for exon 10 in one family. Here we describe the clinical and molecular findings in a severely affected child of this family, homozygous for the 1609delCA and for the M470V polymorphism.
