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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Gene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases

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Montenegro, Marilia M. [1, 2] ; Quaio, Caio R. [1] ; Palmeira, Patricia [3] ; Gasparini, Yanca [2] ; Rangel-Santos, Andreia [3] ; Damasceno, Julian [2] ; Novak, Estela M. [4] ; Gimenez, Thamires M. [5] ; Yamamoto, Guilherme L. [1] ; Ronjo, Rachel S. [1] ; Novo-Filho, Gil M. [1, 2] ; Chehimi, Samar N. [2] ; Zanardo, Evelin A. [2] ; Dias, Alexandre T. [2] ; Nascimento, Amom M. [2] ; Costa, Thais V. M. M. [2] ; Duarte, Alberto J. da S. [2] ; Coutinho, Luiz L. [6] ; Kim, Chong A. [1] ; Kulikowski, Leslie D. [1, 2]
Total Authors: 20
[1] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Unidade Genet, Dept Pediat, Inst Crianca, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med FMUSP, Dept Patol, Lab Citogenom, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Lab Pediat Clin, Dept Pediat, Inst Crianca, Sao Paulo, SP - Brazil
[4] Hemoctr Sao Paulo, Fundacao Prosangue, Sao Paulo, SP - Brazil
[5] Inst Tratamento Canc Infantil ITACI, Lab Pesquisa Translac Oncohematol, Sao Paulo, SP - Brazil
[6] Univ Sao Paulo, ESALQ, Ctr Genom Func, Dept Zootecnia, Piracicaba - Brazil
Total Affiliations: 6
Document type: Journal article
Web of Science Citations: 0

Background Bloom syndrome (BS) is a rare autosomal recessive chromosome instability disorder. The main clinical manifestations are growth deficiency, telangiectasic facial erythema, immunodeficiency, and increased risk to develop neoplasias at early age. Cytogenetic test for sister chromatid exchanges (SCEs) is used as a diagnostic marker for BS. In addition, most patients also present mutations in the \& x202f;BLM \& x202f;gene, related to defects in the DNA repair mechanism. However, the molecular mechanism behind the pathogenicity of BS is \& x202f;still \& x202f;not completely understood. Methods We describe two patients confirmed with BS by SCE and molecular analysis. Also, we performed the gene expression profile by the RNA-seq methodology in mRNA transcripts for differential gene expression analysis using as a biological condition for comparison BS versus health controls. Results We detected 216 differentially expressed genes related to immunological pathways such as positive regulation and activation of B cells, immune effector process and absence of difference of DNA repair genes expression. In addition; we also observed differentially expressed genes associated with apoptosis control, such as BCL2L1, CASP7, CDKN1A, E2F2, ITPR, CD274, TNFAIP6, TNFRSF25, TNFRSF13C, and TNFRSF17. Conclusion Our results suggest that the combination of altered expression of genes involved in signaling pathways of immune response and apoptosis control may contribute directly to the main characteristics observed in BS, such as recurrent infections, growth failure, and high risk of cancer. Transcriptome studies of other instability syndromes could allow a more accurate analysis of the relevant gene interactions associated with the destabilization of the genome. This is a first description of the profile of differential gene expression related to immunological aspects detected in patients with BS by RNA-seq. (AU)

FAPESP's process: 17/08981-1 - Investigation of the cytogenomic profile in 22q11.2 deletion carriers: CNVs x gene expression and immunophenotypic variability
Grantee:Marília Moreira Montenegro
Support type: Scholarships in Brazil - Post-Doctorate