RESUMO
Phenotype of patients with the aprataxin gene mutation varies and according to previous studies, screening of aprataxin gene could be useful, once frataxin gene mutation is excluded in patients with normal GAA expansion in frataxin gene. In the present study, we sought to determine possible causative mutations in aprataxin gene (all exons and flanking intronic sequences) in 14 Greek patients with sporadic cerebellar ataxia all but one without GAA expansion in frataxin gene (1 patient was heterozygous). No detectable point mutation or deletion was found in the aprataxin gene of all the patients. Our results do not confirm the previous studies. This difference may be attributed to the different populations studied and possible different genetic background. It is still questionable whether the screening for aprataxin mutation in Greek patients' Friedreich ataxia phenotype is of clinical importance; larger, multicenter studies are necessary to clarify this issue.
Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação ao Ferro/genética , Mutação , Proteínas Nucleares/genética , Degenerações Espinocerebelares/genética , Repetições de Trinucleotídeos , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Éxons , Grécia , Humanos , Íntrons , Fenótipo , Expansão das Repetições de Trinucleotídeos , Adulto Jovem , FrataxinaRESUMO
A cluster of Friedreich's ataxia patients has been previously investigated in two neighbouring villages of the Paphos district of Cyprus. Molecular genetic studies revealed that all patients had the most common mutation, a homozygous expansion of the GAA triplet repeat in the first intron of the frataxin gene. The present study is aimed at estimating the mutation carrier frequency in the broader area of Paphos. Overall, 1050 individuals originating from the Paphos district took part in the programme. Blood samples were collected for a period of 18 months, on a voluntary basis, after signing a consent form, and analysis of the GAA triplet repeat was performed. The frequency of mutation carriers in the broader area of the Paphos district, and excluding the two neighbouring cluster villages, is estimated to be high. We recommend that an organized prevention programme be implemented to cover the population from this region.
