Screening of targeted panel genes in Brazilian patients with primary ovarian insufficiency

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art_FRANCA_Screening_of_targeted_panel_genes_in_Brazilian_patients_2020.PDF.pdf (990.25 KB)
Citações na Scopus
26
Tipo de produção
article
Data de publicação
2020
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
LERARIO, Antonio M.
SANTOS, Mariza G.
COSTALONGA, Everlayny F.
MACIEL-GUERRA, Andrea T.
Citação
PLOS ONE, v.15, n.10, article ID e0240795, 20p, 2020
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Primary ovarian insufficiency (POI) is a heterogeneous disorder associated with several genes. The majority of cases are still unsolved. Our aim was to identify the molecular diagnosis of a Brazilian cohort with POI. Genetic analysis was performed using a customized panel of targeted massively parallel sequencing (TMPS) and the candidate variants were confirmed by Sanger sequencing. Additional copy number variation (CNV) analysis of TMPS samples was performed by CONTRA. Fifty women with POI (29 primary amenorrhea and 21 secondary amenorrhea) of unknown molecular diagnosis were included in this study, which was conducted in a tertiary referral center of clinical endocrinology. A genetic defect was obtained in 70% women with POI using the customized TMPS panel. Twenty-four pathogenic variants and two CNVs were found in 48% of POI women. Of these variants, 16 genes were identified as BMP8B, CPEB1, INSL3, MCM9, GDF9, UBR2, ATM, STAG3, BMP15, BMPR2, DAZL, PRDM1, FSHR, EIF4ENIF1, NOBOX, and GATA4. Moreover, a microdeletion and microduplication in the CPEB1 and SYCE1 genes, respectively, were also identified in two distinct patients. The genetic analysis of eleven patients was classified as variants of uncertain clinical significance whereas this group of patients harbored at least two variants in different genes. Thirteen patients had benign or no rare variants, and therefore the genetic etiology remained unclear. In conclusion, next-generation sequencing (NGS) is a highly effective approach to identify the genetic diagnoses of heterogenous disorders, such as POI. A molecular etiology allowed us to improve the disease knowledge, guide decisions about prevention or treatment, and allow familial counseling avoiding future comorbidities.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/38224
Referências
  1. Adelman CA, 2013, NATURE, V502, P381, DOI 10.1038/nature12565
  2. Agoulnik AI, 2002, HUM MOL GENET, V11, P3047, DOI 10.1093/hmg/11.24.3047
  3. [Anonymous], 2015, ALZHEIMERS DEMENTI S, V11, pP121
  4. Bennett-Toomey J, 2018, VITAM HORM, V107, P193, DOI 10.1016/bs.vh.2018.01.014
  5. Bertini V, 2010, FERTIL STERIL, V94, DOI 10.1016/j.fertnstert.2010.02.013
  6. Bestetti I, 2019, HUM REPROD, V34, P574, DOI 10.1093/humrep/dey389
  7. Bolcun-Filas E, 2009, PLOS GENET, V5, DOI 10.1371/journal.pgen.1000393
  8. Bouilly J, 2016, J CLIN ENDOCR METAB, V101, P4541, DOI 10.1210/jc.2016-2152
  9. Bouilly J, 2011, HUM MUTAT, V32, P1108, DOI 10.1002/humu.21543
  10. Caburet S, 2014, NEW ENGL J MED, V370, P943, DOI 10.1056/NEJMoa1309635
  11. Patino LC, 2017, SYST BIOL REPROD MED, V63, P145, DOI 10.1080/19396368.2017.1291767
  12. de Boer J, 2002, SCIENCE, V296, P1276, DOI 10.1126/science.1070174
  13. de Vries FAT, 2005, GENE DEV, V19, P1376, DOI 10.1101/gad.329705
  14. de Vries L, 2014, J CLIN ENDOCR METAB, V99, pE2129, DOI 10.1210/jc.2014-1268
  15. Desai S, 2017, J CLIN ENDOCR METAB, V102, P576, DOI 10.1210/jc.2016-2565
  16. Dong JW, 1996, NATURE, V383, P531, DOI 10.1038/383531a0
  17. Eggers S, 2016, GENOME BIOL, V17, DOI 10.1186/s13059-016-1105-y
  18. Franca MM, 2018, CLIN GENET, V93, P408, DOI 10.1111/cge.13156
  19. Franca MM, 2019, EUR J MED GENET, V62, P186, DOI 10.1016/j.ejmg.2018.07.008
  20. Franca MM, 2017, ENDOCRINE, V58, P442, DOI 10.1007/s12020-017-1459-2
  21. Franca MM, 2017, SEX DEV, V11, P137, DOI 10.1159/000477193
  22. Galloway SM, 2000, NAT GENET, V25, P279, DOI 10.1038/77033
  23. Garcia-Rivas G, 2017, BMC MED GENET, V18, DOI 10.1186/s12881-017-0440-5
  24. Huhtaniemi I, 2018, TRENDS ENDOCRIN MET, V29, P400, DOI 10.1016/j.tem.2018.03.010
  25. Ivell R, 2018, HUM REPROD UPDATE, V24, P639, DOI 10.1093/humupd/dmy029
  26. Jaillard S, 2016, J OVARIAN RES, V9, DOI 10.1186/s13048-016-0272-5
  27. Fonseca DJ, 2015, FERTIL STERIL, V104, P154, DOI 10.1016/j.fertnstert.2015.04.016
  28. Jiao X, 2018, TRENDS ENDOCRIN MET, V29, P795, DOI 10.1016/j.tem.2018.07.002
  29. Jung DJ, 2017, NAT COMMUN, V8, DOI 10.1038/ncomms15680
  30. Kasippillai T, 2013, J CLIN ENDOCR METAB, V98, pE1534, DOI 10.1210/jc.2013-1102
  31. Kwon YT, 2003, MOL CELL BIOL, V23, P8255, DOI 10.1128/MCB.23.22.8255-8271.2003
  32. Laissue P, 2018, MOL CELL ENDOCRINOL, V460, P170, DOI 10.1016/j.mce.2017.07.021
  33. Li J, 2012, BIOINFORMATICS, V28, P1307, DOI 10.1093/bioinformatics/bts146
  34. Li Q, 2017, AM J HUM GENET, V100, P267, DOI 10.1016/j.ajhg.2017.01.004
  35. de LaPiscina IM, 2018, FRONT ENDOCRINOL, V9, DOI 10.3389/fendo.2018.00142
  36. McGuire MM, 2011, FERTIL STERIL, V95, P1595, DOI 10.1016/j.fertnstert.2010.12.052
  37. Ohinata Y, 2005, NATURE, V436, P207, DOI 10.1038/nature03813
  38. Qin YY, 2015, HUM REPROD UPDATE, V21, P787, DOI 10.1093/humupd/dmv036
  39. Richards S, 2015, GENET MED, V17, P405, DOI 10.1038/gim.2015.30
  40. Robinson JT, 2011, NAT BIOTECHNOL, V29, P24, DOI 10.1038/nbt.1754
  41. Tay J, 2001, DEV CELL, V1, P201, DOI 10.1016/S1534-5807(01)00025-9
  42. The Lancet, 2020, LANCET PLANET HLTH, V4, pe168
  43. Thorvaldsdottir H, 2013, BRIEF BIOINFORM, V14, P178, DOI 10.1093/bib/bbs017
  44. Tsuiko O, 2016, HUM REPROD, V31, P1913, DOI 10.1093/humrep/dew142
  45. Tucker EJ, 2016, ENDOCR REV, V37, P609, DOI 10.1210/er.2016-1047
  46. Tung JY, 2006, REPROD BIOL ENDOCRIN, V4, DOI 10.1186/1477-7827-4-40
  47. Villaescusa JC, 2006, GENE, V367, P101, DOI 10.1016/j.gene.2005.09.026
  48. Vincent SD, 2014, HUM MOL GENET, V23, P5087, DOI 10.1093/hmg/ddu232
  49. Wang WT, 2015, REPROD BIOMED ONLINE, V31, P573, DOI 10.1016/j.rbmo.2015.06.012
  50. Webber L, 2016, HUM REPROD, V31, P926, DOI 10.1093/humrep/dew027
  51. Wood-Trageser MA, 2014, AM J HUM GENET, V95, P754, DOI 10.1016/j.ajhg.2014.11.002
  52. Yan OY, 2006, MUTAT RES-FUND MOL M, V596, P64, DOI 10.1016/j.mrfmmm.2005.12.016
  53. Ying Y, 2000, MOL ENDOCRINOL, V14, P1053, DOI 10.1210/me.14.7.1053
  54. Zappavigna V, 2004, P NATL ACAD SCI USA, V101, P14800, DOI 10.1073/pnas.0406451101
  55. Zhang W, 2018, REPROD BIOMED ONLINE, V36, P206, DOI 10.1016/j.rbmo.2017.10.104
  56. Zhao GQ, 1996, GENE DEV, V10, P1657, DOI 10.1101/gad.10.13.1657

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MOG
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/42
Artigos e Materiais de Revistas Científicas - LIM/58