title: BAK, BAX, and NBK/BIK proapoptotic gene alterations in Iranian patients with ataxia telangiectasia.
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. isaiian@sina.tums.ac.ir
authors.forename: Anna
authors.initials: A
authors.lastname: Isaian
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Bogdanova
authors.forename: Masoud
authors.initials: M
authors.lastname: Houshmand
authors.forename: Masoud
authors.initials: M
authors.lastname: Movahadi
authors.forename: Asghar
authors.initials: A
authors.lastname: Aghamohammadi
authors.forename: Asghar
authors.initials: A
authors.lastname: Agamohammadi
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.forename: Lida
authors.initials: L
authors.lastname: Atarod
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Sadeghi-Shabestari
authors.forename: Seyed Hasan
authors.initials: SH
authors.lastname: Tonekaboni
authors.forename: Zahra
authors.initials: Z
authors.lastname: Chavoshzadeh
authors.forename: Seyed Mohammad Seyed
authors.initials: SM
authors.lastname: Hassani
authors.forename: Reza
authors.initials: R
authors.lastname: Mirfakhrai
authors.forename: Taher
authors.initials: T
authors.lastname: Cheraghi
authors.forename: Najmoddin
authors.initials: N
authors.lastname: Kalantari
authors.forename: Mitra
authors.initials: M
authors.lastname: Ataei
authors.forename: Thilo
authors.initials: T
authors.lastname: Dork-Bousset
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Sanati
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000276:immunology; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D047668:Inteins / Q000235:genetics; D007492:Iran; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D024101:Mitochondrial Proteins; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics* / Q000276:immunology; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000276:immunology
chemical_list: D051017:Apoptosis Regulatory Proteins; C494772:BAK1 protein, human; C096820:BIK protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein