Cytogenetic diagnosis of patients with suspected premature ovarian failure in Manaus, Brazil

Authors

  • Ruan Barboza Rocha Laboratório de Citogenética Humana, Universidade do Estado do Amazonas, Manaus, Brasil
  • Denise Corrêa Benzaquem Laboratório de Citogenética Humana, Universidade do Estado do Amazonas, Manaus, Brasil
  • Paloma de Sousa Passos Laboratório de Citogenética Humana, Universidade do Estado do Amazonas, Manaus, Brasil
  • Evellyn Karine Cruz da Silva Laboratório de Citogenética Humana, Universidade do Estado do Amazonas, Manaus, Brasil
  • Natália Dayane Moura Carvalho Instituto de Saúde e Biotecnologia, Universidade Federal do Amazonas, Coari, Brasil
  • Daria Barroso Serrão das Neves Departamento de Ginecologia, Universidade do Estado do Amazonas, Manaus, Brasil
  • Paula Rita Leite da Silva Departamento de Ginecologia, Universidade do Estado do Amazonas, Manaus, Brasil
  • Cleiton Fantin Laboratório de Citogenética Humana, Universidade do Estado do Amazonas, Manaus, Brasil

DOI:

https://doi.org/10.36253/caryologia-3030

Keywords:

chromosomal alterations, X chromosome, medical diagnosis, Premature Ovarian Failure, G-band karyotype

Abstract

Premature ovarian failure (POF) is a clinical syndrome that is characterized by loss of ovarian function in women of childbearing age and generally occurs before the age of 40. Genetic causes account for about 20 to 25% of cases of POF. However, in many cases, the origin of the condition remains idiopathic. The objective of this study was to perform cytogenetic research in a group of patients affected by POF in order to identify the type and frequency of chromosomal alterations. Fifteen patients were referred to the Human Cytogenetics Laboratory of the Amazonas State University (UEA) by gynecology specialists from two public health institutions in Manaus, Amazonas, Brazil, for chromosomal analysis. The analysis was performed via peripheral blood lymphocyte culture using the GTG banding method. The karyotypes were assembled with the help of the GeneAll-HD® software and the results were interpreted according to the ISCN 2016 standards. Of the fifteen patients analyzed, nine (60%) had no chromosomal abnormalities, while six (40%) exhibited chromosomal abnormalities. Of the alterations identified, three patients (20%) presented numerical alterations of the X chromosome with mosaicism, two patients (13%) showed autosomal numerical alterations involving chromosomes 15 and 21, both with mosaicism, and one patient (7%) exhibited a structural alteration in the form of terminal deletion of the long arm of the X chromosome. The results obtained in this study have the potential to improve the accuracy of the diagnosis, assist in medical decisions, provide adequate prognoses and facilitate reproductive management through genetic counseling.

Downloads

Download data is not yet available.

References

Albright F, Smith PH, Fraser R. 1942. A syndrome characterized by primary ovarian insufficiency and decreased stature: Report of 11 cases with a digression on hormonal control of axillary and pubic hair. Am J Med Sci. 204(5):625–648. https://doi.org/10.1097/00000441-194211000-00001.

Ayed W, Amouri A, Hammami W, Kilani O, Turki Z, Harzallah F, Bouayed-Abdelmoula N, Chemkhi I, Zhioua F, Slama CB, et al. 2014. Cytogenetic abnormalities in Tunisian women with premature ovarian failure. C R Biol. 337(12):691–694. https://doi.org/10.1016/j.crvi.2014.09.003.

Baronchelli S, Conconi D, Panzeri E, Bentivegna A, Redaelli S, Lissoni S, Saccheri F, Villa N, Crosti F, Sala E, et al. 2011. Cytogenetics of premature ovarian failure: an investigation on 269 affected women. J Biomed Biotechnol. 2011(1):370195. https://doi.org/10.1155/2011/370195.

Barros F, Carvalho F, Barros A, Dória S, et al. 2020. Premature ovarian insufficiency: clinical orientations for genetic testing and genetic counseling. Porto Biomed J. 5(3):e62. https://doi.org/10.1097/j.pbj.0000000000000062.

Beke A, Piko H, Haltrich I, Csomor J, Matolcsy A, Fekete G, Rigo J, Karcagi V, et al. 2013. Molecular cytogenetic analysis of Xq critical regions in premature ovarian failure. Mol Cytogenet. 6(1):62. https://doi.org/10.1186/1755-8166-6-62.

Bertini V, Viola D, Vitti P, Simi P, Valetto A, et al. 2012. An idic(15) associated with POF (premature ovarian failure): Molecular cytogenetic definition of a case and review of the literature. Gene. 503(1):123–125. https://doi.org/10.1016/j.gene.2012.04.071.

Besson M da R, Taiarol M dos S, Fernandes EB, Ghiorzi IB, Nunes MR, Zen PRG, Rosa RFM, et al. 2023. Chromosomal abnormalities detected by karyotyping among patients with secondary amenorrhea: a retrospective study. Sao Paulo Med J. 141(5). https://doi.org/10.1590/1516-3180.2022.0426.r1.14012023.

Geckinli, Toksoy, Sayar, Soylemez, Yesil, Aydın, Karaman, Devranoglu, et al. 2014. Prevalence of X-aneuploidies, X-structural abnormalities and 46,XY sex reversal in Turkish women with primary amenorrhea or premature ovarian insufficiency. Eur J Obstet Gynecol Reprod Biol. 182:211–215. https://doi.org/10.1016/j.ejogrb.2014.09.033.

Ceylaner G, Altinkaya SO, Mollamahmutoglu L, Ceylaner S, et al. 2010. Genetic abnormalities in Turkish women with premature ovarian failure. Int J Gynecol Amp Obstet. 110(2):122–124. https://doi.org/10.1016/j.ijgo.2010.03.023.

Chen M, Jiang H, Zhang C. 2023. Selected Genetic Factors Associated with Primary Ovarian Insufficiency. Int J Mol Sci. 24(5):4423. https://doi.org/10.3390/ijms24054423.

Chon SJ, Umair Z, Yoon MS. 2021. Premature Ovarian Insufficiency: Past, Present, and Future. Front Cell Dev Biol. 9. https://doi.org/10.3389/fcell.2021.672890.

Cordts EB, Christofolini DM, dos Santos AA, Bianco B, Barbosa CP, et al. 2010. Genetic aspects of premature ovarian failure: a literature review. Arch Gynecol Obstet. 283(3):635–643. https://doi.org/10.1007/s00404-010-1815-4.

Davison RM, Davis CJ, Conway GS. 1999. The X chromosome and ovarian failure. Clin Endocrinol. 51(6):673–679. https://doi.org/10.1046/j.1365-2265.1999.00926.x.

Di-Battista A, Moysés-Oliveira M, Melaragno MI. 2020. Genetics of premature ovarian insufficiency and the association with X-autosome translocations. Reproduction. 160(4):R55—R64. https://doi.org/10.1530/rep-20-0338.

ESHRE. 2016. Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 31(5):926–937. https://doi.org/10.1093/humrep/dew027.

Ferrarini E, Russo L, Fruzzetti F, Agretti P, De Marco G, Dimida A, Gianetti E, Simoncini T, Simi P, Baldinotti F, et al. 2013. Clinical characteristics and genetic analysis in women with premature ovarian insufficiency. Maturitas. 74(1):61–67. https://doi.org/10.1016/j.maturitas.2012.09.017.

Franić D. et al. 2016. Genetic Etiology of Primary Premature Ovarian Insufficiency. Acta Clin Croat. 629–635. https://doi.org/10.20471/acc.2016.55.04.14.

Gersak K, Veble A. 2011. Low-level X chromosome mosaicism in women with sporadic premature ovarian failure. Reprod Biomed Online. 22(4):399–403. https://doi.org/10.1016/j.rbmo.2011.01.002.

Goswami D, Conway GS. 2005. Premature ovarian failure. Hum Reprod Update. 11(4):391–410. https://doi.org/10.1093/humupd/dmi012.

Holland CM. 2001. 47,XXX in an Adolescent with Premature Ovarian Failure and Autoimmune Disease. J Pediatr Adolesc Gynecol. 14(2):77–80. https://doi.org/10.1016/s1083-3188(01)00075-4.

Hosseini S, Vahid Dastjerdi M, Asgari Z, Samiee H, et al. 2011. Premature ovarian failure in a woman with a balanced 15;21 translocation: a case report. J Med Case Rep. 5(1). https://doi.org/10.1186/1752-1947-5-250.

Ishizuka B. 2021. Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI). Front Endocrinol. 12. https://doi.org/10.3389/fendo.2021.626924.

Issa NM, Elhady GM. 2022. Cytogenetic abnormalities in a sample of females with premature ovarian failure. Middle East Fertil Soc J. 27(1). https://doi.org/10.1186/s43043-022-00098-3.

Jankowska K. 2017. Premature ovarian failure. Menopausal Rev. 2:51–56. https://doi.org/10.5114/pm.2017.68592.

Jiao X, Qin C, Li J, Qin Y, Gao X, Zhang B, Zhen X, Feng Y, Simpson JL, Chen Z-J, et al. 2012. Cytogenetic analysis of 531 Chinese women with premature ovarian failure. Hum Reprod. 27(7):2201–2207. https://doi.org/10.1093/humrep/des104.

Jin M, Yu Y, Huang H. 2012. An update on primary ovarian insufficiency. Sci China Life Sci. 55(8):677–686. https://doi.org/10.1007/s11427-012-4355-2.

Kalantari H, Madani T, Zari Moradi S, Mansouri Z, Almadani N, Gourabi H, Mohseni Meybodi A et al. 2013. Cytogenetic analysis of 179 Iranian women with premature ovarian failure. Gynecol Endocrinol. 29(6):588–591. https://doi.org/10.3109/09513590.2013.788625.

Lakhal B, Braham R, Berguigua R, Bouali N, Zaouali M, Chaieb M, Veitia RA, Saad A, Elghezal H, et al 2010. Cytogenetic analyses of premature ovarian failure using karyotyping and interphase fluorescence in situ hybridization (FISH) in a group of 1000 patients. Clin Genet. 78(2):181–185. https://doi.org/10.1111/j.1399-0004.2009.01359.x.

Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N, et al. 2003. Premature menopause in a multi-ethnic population study of the menopause transition. Hum Reprod. 18(1):199–206. https://doi.org/10.1093/humrep/deg005.

Luo W, Ke H, Tang S, Jiao X, Li Z, Zhao S, Zhang F, Guo T, Qin Y, et al. 2023. Next-generation sequencing of 500 POI patients identified novel responsible monogenic and oligogenic variants. J Ovarian Res. 16(1). https://doi.org/10.1186/s13048-023-01104-6.

McGowan-Jordan J, Simons A, Schmid M, editors. 2016. ISCN 2016: An international system for human cytogenomic nomenclature (2016). S. Karger AG. https://doi.org/10.1159/isbn.978-3-318-06861-0.

Moorhead PS, Nowell PC, Mellman WJ, Battips DM, Hungerford DA, et al. 1960. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res. 20(3):613–616. https://doi.org/10.1016/0014-4827(60)90138-5.

Neves AR, Pais AS, Ferreira SI, Ramos V, Carvalho MJ, Estevinho A, Matoso E, Geraldes F, Marques Carreira I, Águas F, et al. 2021. Prevalence of cytogenetic abnormalities and FMR1 gene premutation in a Portuguese population with premature ovarian insufficiency. Acta Med Port. 34(9):580–585. https://doi.org/10.20344/amp.13490.

Persani L, Rossetti R, Cacciatore C, Bonomi M, et al. 2009. Primary ovarian insufficiency: X chromosome defects and autoimmunity. J Autoimmun. 33(1):35–41. https://doi.org/10.1016/j.jaut.2009.03.004.

Podfigurna-Stopa A, Czyzyk A, Grymowicz M, Smolarczyk R, Katulski K, Czajkowski K, Meczekalski B, et al. 2016. Premature ovarian insufficiency: the context of long-term effects. J Endocrinol Invest. 39(9):983–990. https://doi.org/10.1007/s40618-016-0467-z.

Portnoi MF, Aboura A, Tachdjian G, Bouchard P, Dewailly D, Bourcigaux N, Fridman R, Christin-Maitre S, et al. 2006. Molecular cytogenetic studies of Xq critical regions in premature ovarian failure patients. Hum Reprod. 21(9):2329–2334. https://doi.org/10.1093/humrep/del174.

Powell CM, Taggart RT, Drumheller TC, Wangsa D, Qian C, Nelson LM, White BJ, et al. 1994. Molecular and cytogenetic studies of an X;autosome translocation in a patient with premature ovarian failure and review of the literature. Am J Med Genet. 52(1):19–26. https://doi.org/10.1002/ajmg.1320520105.

Qin Y, Jiao X, Simpson JL, Chen ZJ, et al. 2015. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update. 21(6):787–808. https://doi.org/10.1093/humupd/dmv036.

Rahman R, Panay N. 2021. Diagnosis and management of premature ovarian insufficiency. Best Pract Amp Res Clin Endocrinol Amp Metab. 35(6):101600. https://doi.org/10.1016/j.beem.2021.101600.

Rosa RFM, Dibi RP, Picetti J dos S, Rosa RCM, Zen PRG, Graziadio C, Paskulin GA, et al. 2008. Amenorréia e anormalidades do cromossomo X. Rev Bras Ginecol Obstet. 30(10). https://doi.org/10.1590/s0100-72032008001000006.

Rudnicka E, Kruszewska J, Klicka K, Kowalczyk J, Grymowicz M, Skórska J, Pięta W, Smolarczyk R, et al. 2018. Premature ovarian insufficiency – aetiopathology, epidemiology, and diagnostic evaluation. Prz Menopauzalny. 17(3):105–108. https://doi.org/10.5114/pm.2018.78550.

Sala C, Arrigo G, Torri G, Martinazzi F, Riva P, Larizza L, Philippe C, Jonveaux P, Sloan F, Labella T, et al. 1997. Eleven X chromosome breakpoints associated with premature ovarian failure (POF) map to a 15-Mb YAC contig spanning Xq21. Genomics. 40(1):123–131. https://doi.org/10.1006/geno.1996.4542.

Seabright M. 1973. High resolution studies on the pattern of induced exchanges in the human karyotype. Chromosoma. 40(4):333–346. https://doi.org/10.1007/bf00399426.

Sybert VP, McCauley E. 2004. Turner’s Syndrome. New Engl J Med. 351(12):1227–1238. https://doi.org/10.1056/nejmra030360.

Turkyilmaz A, Alavanda C, Ates EA, Geckinli BB, Polat H, Gokcu M, Karakaya T, Cebi AH, Soylemez MA, Guney Aİ, et al. 2022. Whole-exome sequencing reveals new potential genes and variants in patients with premature ovarian insufficiency. J Assist Reprod Genet. 39(3):695–710. https://doi.org/10.1007/s10815-022-02408-0.

Van Kasteren YM, Hundscheid RDL, Smits APT, Cremers FPM, van Zonneveld P, Braat DDM, et al. 1999. Familial idiopathic premature ovarian failure: an overrated and underestimated genetic disease? Hum Reprod. 14(10):2455–2459. https://doi.org/10.1093/humrep/14.10.2455.

Wesevich V, Kellen AN, Pal L. 2020. Recent advances in understanding primary ovarian insufficiency. F1000Research. 9:1101. https://doi.org/10.12688/f1000research.26423.1.

Zeng J, Huang W, Huang M, Wang Z. 2019. The first report showing de novo partial 21q monosomy in an adult woman with occult primary ovarian insufficiency (POI). Clin Chem Lab Med (CCLM). 57(9):e230-e233. https://doi.org/10.1515/cclm-2018-1271.

Zinn AR. 2001. The X Chromosome and the Ovary. J Soc Gynecol Investig. 8(1_suppl):S34—S36. https://doi.org/10.1177/1071557601008001s11.

Downloads

Published

2025-10-07

How to Cite

Barboza Rocha, R., Corrêa Benzaquem, D., de Sousa Passos, P., Karine Cruz da Silva, E., Dayane Moura Carvalho, N., Barroso Serrão das Neves, D., … Fantin, C. (2025). Cytogenetic diagnosis of patients with suspected premature ovarian failure in Manaus, Brazil. Caryologia, 78(1), 59–66. https://doi.org/10.36253/caryologia-3030

Issue

Vol. 78 No. 1 (2025)

Section

Articles

License

Copyright (c) 2025 Ruan Barboza Rocha, Denise Corrêa Benzaquem, Paloma de Sousa Passos, Evellyn Karine Cruz da Silva, Natália Dayane Moura Carvalho, Daria Barroso Serrão das Neves, Paula Rita Leite da Silva, Cleiton Fantin

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

  • Copyright on any open access article in a journal published byCaryologia is retained by the author(s).
  • Authors grant Caryologia a license to publish the article and identify itself as the original publisher.
  • Authors also grant any third party the right to use the article freely as long as its integrity is maintained and its original authors, citation details and publisher are identified.
  • The Creative Commons Attribution License 4.0 formalizes these and other terms and conditions of publishing articles.
  • In accordance with our Open Data policy, the Creative Commons CC0 1.0 Public Domain Dedication waiver applies to all published data in Caryologia open access articles.