Emphasis Type="Italic"BAK/Emphasis Emphasis

Authors: Anna Isaian Natalia V Bogdanova Masoud Houshmand Masoud Movahadi Asghar Agamohammadi Nima Rezaei Lida Atarod Mahnaz SadeghiShabestari Seyed Hasan Tonekaboni Zahra Chavoshzadeh Seyed Mohammad Seyed Hassani Reza Mirfakhrai Taher Cheraghi Najmoddin Kalantari Mitra Ataei Thilo DorkBousset Mohammad Hossein Sanati

Publish Date: 2009/11/07

Volume: 30, Issue: 1, Pages: 132-137

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Abstract

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 diseaseFifty 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 BiosystemsEight 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 = 00001 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  00001 Sequence alteration in intronic region of the NBK/BIK gene IVS412delTC was observed in 52 of AT patients which was significantly higher than 20 in the control group P = 00023 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  00001 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  00001Several 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 patientsThe authors are very grateful for all colleagues in Medical School of Hannover Hannover Germany for their kind help and advices in the laboratory and all the patients and their families for their kind collaboration in this study We would like to thank Dr Ali Rabbani for his help and support

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