Open AccessGene expression profile suggesting immunological dysregulation in two Brazilian Bloom's syndrome cases
Author(s) -
Montenegro Marilia M.,
Quaio Caio R.,
Palmeira Patricia,
Gasparini Yanca,
RangelSantos Andreia,
Damasceno Julian,
Novak Estela M.,
Gimenez Thamires M.,
Yamamoto Guilherme L.,
Ronjo Rachel S.,
NovoFilho Gil M.,
Chehimi Samar N.,
Zanardo Evelin A.,
Dias Alexandre T.,
Nascimento Amom M.,
Costa Thais V. M. M.,
Duarte Alberto J. da S.,
Coutinho Luiz L.,
Kim Chong A.,
Kulikowski Leslie D.
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1133
Subject(s) - biology , gene , transcriptome , bloom syndrome , genetics , gene expression , chromosome instability , genome instability , immune system , immune dysregulation , dna repair , chromosome , dna damage , dna , rna , helicase
Abstract 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 BLM gene, related to defects in the DNA repair mechanism. However, the molecular mechanism behind the pathogenicity of BS is still 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 TNFRSF 17. 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.