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

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Citações na Scopus
6
Tipo de produção
article
Data de publicação
2020
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ISSN da Revista
Título do Volume
Editora
WILEY
Citação
MOLECULAR GENETICS & GENOMIC MEDICINE, v.8, n.4, article ID e1133, 10p, 2020
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Unidades Organizacionais
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Resumo
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.
Palavras-chave
BLM gene, Transcriptome, Bloom's syndrome, Immunology, RNA-Seq
Referências
  1. Amor-Gueret M, 2006, CANCER LETT, V236, P1, DOI 10.1016/j.canlet.2005.04.023
  2. Beamish H, 2002, J BIOL CHEM, V277, P30515, DOI 10.1074/jbc.M203801200
  3. Bhisitkul RB, 2004, BRIT J OPHTHALMOL, V88, P354, DOI 10.1136/bjo.2002.011643
  4. BLOOM D, 1954, AMA AM J DIS CHILD, V88, P754, DOI 10.1001/archpedi.1954.02050100756008
  5. Brosh RM, 2001, J BIOL CHEM, V276, P3024, DOI 10.1074/jbc.M006784200
  6. Chakraverty RK, 1999, BIOESSAYS, V21, P286
  7. Chen K, 2019, OXID MED CELL LONGEV, V2019, DOI 10.1155/2019/3685817
  8. Cunniff C, 2017, MOL SYNDROMOL, V8, P4, DOI 10.1159/000452082
  9. Derks KWJ, 2014, DNA REPAIR, V19, P214, DOI 10.1016/j.dnarep.2014.03.008
  10. Ellis NA, 1998, AM J HUM GENET, V63, P1685, DOI 10.1086/302167
  11. ELLIS NA, 1995, CELL, V83, P655, DOI 10.1016/0092-8674(95)90105-1
  12. Elmore S, 2007, TOXICOL PATHOL, V35, P495, DOI 10.1080/01926230701320337
  13. Flanagan M, 2006, GENEREVIEWS
  14. GERMAN J, 1989, CLIN GENET, V35, P57
  15. German J, 1997, CANCER GENET CYTOGEN, V93, P100, DOI 10.1016/S0165-4608(96)00336-6
  16. GERMAN J, 1969, AM J HUM GENET, V21, P196
  17. GERMAN J, 1993, MEDICINE, V72, P393, DOI 10.1097/00005792-199311000-00003
  18. Goudy K, 2013, CLIN IMMUNOL, V146, P248, DOI 10.1016/j.clim.2013.01.004
  19. Hickson ID, 2001, BIOCHEM SOC T, V29, P201, DOI 10.1042/0300-5127:0290201
  20. Huang DW, 2009, NAT PROTOC, V4, P44, DOI 10.1038/nprot.2008.211
  21. Kaneko H, 2011, MOL MED REP, V4, P607, DOI 10.3892/mmr.2011.484
  22. Kvam VM, 2012, AM J BOT, V99, P248, DOI 10.3732/ajb.1100340
  23. Langmead B, 2012, NAT METHODS, V9, P357, DOI [10.1038/NMETH.1923, 10.1038/nmeth.1923]
  24. Li H, 2009, BIOINFORMATICS, V25, P1754, DOI 10.1093/bioinformatics/btp324
  25. Liu Y, 2008, GENE DEV, V22, P2737, DOI 10.1101/gad.1732808
  26. Ma B, 2001, ANN ONCOL, V12, P1015, DOI 10.1023/A:1011106202939
  27. Moreira Marilia Borges, 2013, J Med Case Rep, V7, P284, DOI 10.1186/1752-1947-7-284
  28. Morimoto W, 2002, INT J MOL MED, V10, P95
  29. Resende Ana Cristina Brandão de, 2007, An. Bras. Dermatol., V82, P363, DOI 10.1590/S0365-05962007000400011
  30. Sanz M. M., 2016, BLOOMS SYNDROME
  31. Schoenaker MHD, 2018, J CLIN IMMUNOL, V38, P35, DOI 10.1007/s10875-017-0454-y
  32. Wang XB, 2008, J HUAZHONG U SCI-MED, V28, P46, DOI 10.1007/s11596-008-0111-z