Frequency of the Δf508 Mutation in 108 Cystic Fibrosis Patients in São Paulo: Comparison With Reported Brazilian Data

Abstract

OKAY TS et al. Frequency of the ∆f508 mutation in 108 cystic fibrosis patients in São Paulo: comparison with reported Brazilian data. CLINICS 60(2):131-134, 2005. PURPOSE:To analyze the frequency of the delta F508 (∆F508) deletion mutation in 108 unrelated cystic fibrosis patients and compare the results with the previously reported data for Brazilian patients. Cystic fibrosis is the leading cause of genetic disease in Caucasians, and the ∆F508 deletion is the most common mutation associated with the disease.METHOD: The frequency of the ∆F508 mutation was assessed by means of a polymerase chain reaction (PCR) followed by detection in 8% silver-stained polyacrylamide gels.RESULTS: Twenty-three of 108 patients (21.3%) were homozygous for the ∆F508 deletion, 50 were heterozygous (46.3%), and the remaining 35 (32.4%) were non-carriers. In terms of alleles, there were 96 mutated (96/216 or 44.45%) and 120 wild-type ones (120/216 or 55.5%).CONCLUSION: The 44.45% of affected alleles that were found is higher than the 33% first described in 1993, but slightly lower than the 48% recently reported. Moreover, our data corroborated the idea that the frequency of the ∆F508 mutation is lower in Brazil in comparison to that found in studies carried out in Europe and North American (circa 70.0%), probably due to increased racial miscegenation. These findings must be taken into account before any genetic screening of the population is proposed in Brazil. CLINICS 60(2):131-134, 2005 Frequency of the ∆F508 mutation in 108 cystic fibrosis patients in são paulo Okay TS et al.

Canais Iônicos E Fibrose Cística

“…O mutante delta F508 (F508) faz parte desta classe; ele não promove uma dobra suficiente para permitir sua saída do RE (5) , e, em consequência, a proteína será degradada dentro da organela ao invés de prosseguir às células secretoras para exercer suas funções (25) . É o defeito mais comum, contribuindo com cerca de 70% de todos os alelos FC nas populações caucasianas (4,5,7,12,17) .…”

“…A primeira mutação de FC identificada foi a F508 que consiste em uma deleção de três pares de bases nitrogenadas no éxon 10 do gene FC e acarreta a ausência de um resíduo de aminoácido (fenilalanina) na posição 508 da proteína codificada pelo gene (4,5,7,12) . Esta mutação ocorre em aproximadamente 70% dos cromossomos FC no…”

“…Norte da Europa e nos Estados Unidos da América, embora tenha sido demonstrado que a frequência desta mutação sofre variações, principalmente entre grupos étnicos, 3 variando de 26% na Turquia a 88% na Dinamarca (12) (27) . desenvolvimento da doença pulmonar na FC (27) .…”

“…O diagnóstico é baseado nos achados clínicos, e confirmado pela demonstração laboratorial de concentrações anormalmente elevadas de cloreto no suor (> 60 mlEq/ l) (7,8,12) e pela análise genética (7,13) . O aumento da suspeição clínica e o diagnóstico através de análise genética têm levado à identificação de pacientes adolescentes e adultos com esta patologia (13,14) .…”

In the April 2005 Issue of Clinics

“…Okay et al 7 analyzed the frequency of the Df508 mutation in 108 cystic fibrosis patients in São Paulo, in comparison with reported Brazilian data. Cystic fibrosis is the leading cause of genetic disease in Caucasians, and the DF508 deletion is the most common mutation associated with the disease.…”