RESUMEN
INTRODUCTION: Ataxia telangiectasia (AT) is an autosomal recessive multisystem disorder characterized by variable immunodeficiency, progressive neurodegeneration, occulocutaneous telangiectasia, and an increased susceptibility to malignancies. This study was designed to study the role of proapoptotic BAK, BAX, and NBK/BIK genes in a group of patients with AT to elucidate the possible role of these genes in progression of malignancies in this disease. MATERIALS AND METHODS: Fifty Iranian patients with AT were investigated in this study. The entire coding regions of the BAK gene (exons 2-6), NBK/BIK gene (exons 2-5), and BAX gene (exons 1-7) were amplified using polymerase chain reaction (PCR). The PCR products were separated by 2% agarose gel electrophoresis, and all positive samples were verified by direct sequencing of PCR products using the same primers used for PCR amplification, BigDye chemistry, and Avent 3100 Genetic Analyzer following the manufacturer's instructions (Applied Biosystems). RESULTS: Eight of fifty Iranian AT patients (16%) exhibited a C > T transition in exon 2 (c342C > T) of the BAK gene, while none of the healthy controls had such alteration (P = 0.0001). Higher frequency of another nucleotide substitution in the noncoding region of exon 7 in BAX gene (6855G > A) was also identified in 68% of the patient group versus 24% in the controls (P < 0.0001). Sequence alteration in intronic region of the NBK/BIK gene IVS4-12delTC was observed in 52% of AT patients, which was significantly higher than 20% in the control group (P = 0.0023). Another variant IVS1146C > T in the intronic region of the BAX gene was found in 78% of patients, which was significantly higher than 10% in the controls (P < 0.0001). Frequency of alteration in intronic region of exon 3 of the BAX gene (IVS3 + 14A > G) was also significantly higher in the AT patients (P < 0.0001). DISCUSSION: Several alterations in the proapoptotic genes BAK, NBK/BIK, and BAX were found in our study, which could elucidate involvement of the mitochondrial pathway mediated apoptosis in accelerating and developing of cancers and in immunopathogenesis of AT. Such altered apoptosis in AT could play some roles in developing cancers in this group of patients.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/inmunología , Proteínas de la Membrana/genética , Proteína Destructora del Antagonista Homólogo bcl-2/genética , Proteína X Asociada a bcl-2/genética , Adolescente , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/inmunología , Ataxia Telangiectasia/fisiopatología , Niño , Análisis Mutacional de ADN , Progresión de la Enfermedad , Exones/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Inteínas/genética , Irán , Masculino , Proteínas de la Membrana/inmunología , Proteínas Mitocondriales , Mutación/genética , Polimorfismo Genético , Proteína Destructora del Antagonista Homólogo bcl-2/inmunología , Proteína X Asociada a bcl-2/inmunologíaRESUMEN
An evaluation was conducted on the knowledge gained by pediatric residents on CPR, before and after a PALS (Pediatric Advanced Cardiac Life Support) course. Following an examination of all pediatric residents at Tehran University of Medical Sciences, they were divided into two groups: non-trained (Group 1) and a group scheduled to undergone training (Group 2). A course on ACLS was conducted. Examination were performed before and after the ACLS course. The mean of the examination prior to the course in Group 1 and 2 was low, reflecting no significant differences between the Groups. Examination after the ACLS course showed a statistically significant improvement in Group 2 (P < or = 0.05). It is concluded that knowledge of pediatric residents was low before ACLS course and enhanced after the course.