Prevalência de mosaicismo cromossômico em 2.500 casos realizados em um laboratório de genética no Estado do Rio de Janeiro, Brasil

Mauricio Assis Rodrigues; Bianca Rodrigues Marques Peterle; Erick de Souza Costa; Antonio Francisco Alves da Silva; Patricia Damasceno Ribeiro

doi:10.19180/1809-2667.v22n32020p579-589

Authors

Mauricio Assis Rodrigues XY Diagnose Laboratório de Biotecnologia, Campos dos Goytacazes/RJ
Bianca Rodrigues Marques Peterle Universidade Federal do Espírito Santo (UFES), Vitória/ES
Erick de Souza Costa Bedalab Laboratório de Análises Clínicas, Campos dos Goytacazes/RJ
Antonio Francisco Alves da Silva XY Diagnose Laboratório de Biotecnologia, Campos dos Goytacazes/RJ
Patricia Damasceno Ribeiro XY Diagnose Laboratório de Biotecnologia, Campos dos Goytacazes/RJ

DOI:

https://doi.org/10.19180/1809-2667.v22n32020p579-589

Keywords:

Cytogenetcis, Chromosomal Aberrations, Chromosomal Mosaicism, Genetics

Abstract

Chromosomal mosaicism is defined as the presence of two or more cell lines with different chromosomal constitutions in the same individual. The present study aims to analyze the prevalence of chromosomal mosaicisms from 2,500 patients who underwent a cytogenetic study carried out in a genetics laboratory located in a city of the Rio de Janeiro State from 04/2011 to 01/2020. Of the 2,500 karyotype exams analyzed, 19 presented chromosomal mosaicisms, nine of which were female, eight male and two undefined. Regarding the type, the study found 14 cases of numerical chromosome aberrations and five cases of structural chromosome aberrations. Infertility was the most prevalent clinical indication, totaling seven patients. Among the 19 cases in this study, two were published in scientific journals. Chromosomal mosaicism can present cell lines with very variable percentages. For greater security, it suggests counting a larger number of cells to increase the chance of identifying these aberrations.

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Author Biographies

Mauricio Assis Rodrigues, XY Diagnose Laboratório de Biotecnologia, Campos dos Goytacazes/RJ

Coordenador do setor de Citogenética Humana do XY Diagnose Laboratório de Biotecnologia em Campos dos Goytacazes/RJ. Mestrando em Biociências e Biotecnologia na Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF) – Campos dos Goytacazes/RJ – Brasil. E-mail: mauricioassis@hotmail.com.
Bianca Rodrigues Marques Peterle, Universidade Federal do Espírito Santo (UFES), Vitória/ES

Professora no Centro Educacional Leonardo da Vinci. Mestrado profissional em Química no Instituto Federal Espírito Santo (IFES) Campus Vila Velha/ES – Brasil. E-mail: biancapeterle@yahoo.com.br.
Erick de Souza Costa, Bedalab Laboratório de Análises Clínicas, Campos dos Goytacazes/RJ

Supervisor técnico e gerente da qualidade do Bedalab Laboratório de Análises Clínicas em Campos dos Goytacazes/RJ. Pós-graduação em Análises Clínicas e Microbiologia pela Universidade Candido Mendes (UCAM) – Campos dos Goytacazes/RJ – Brasil. E-mail: ecosta_souza@hotmail.com.
Antonio Francisco Alves da Silva, XY Diagnose Laboratório de Biotecnologia, Campos dos Goytacazes/RJ

Referência técnica do Departamento de Genética Molecular do XY Diagnose Laboratório de Genética em Campos dos Goytacazes/RJ. Doutor (2016) em Biociências e Biotecnologia pela Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF) – Campos dos Goytacazes/RJ – Brasil. E-mail: antonio.alves@xydiagnose.com.br.
Patricia Damasceno Ribeiro, XY Diagnose Laboratório de Biotecnologia, Campos dos Goytacazes/RJ

Responsável técnico pelo XY Diagnose Laboratório de Biotecnologia em Campos dos Goytacazes/RJ, assessora científica da UTI Neonatal Nicola Albano e professora titular de Genética e Bioquímica da UNIG Campus V – Itaperuna/RJ. Doutora em Engenharia Genética (2003) pela Universidade Estadual do Norte Fluminense Darcy Ribeiro (UENF) – Campos dos Goytacazes/RJ – Brasil. E-mail: pd_ribeiro@hotmail.com.

References

AL-ACHKAR, W. et al. Detailed analysis of an idic(Y)(q11.21) in a mosaic karyotype. Mol Med Rep, Athens, v. 6, p. 293-296, 2012. Disponível em: https://www.spandidos-publications.com/10.3892/mmr.2012.930. Acesso em: 10 jan. 2020.

ALLANSON, J. E.; GRAHAM, G. E. Principles and Practice of Medical Genetics. 4th. ed. Churchill Livingstone, Edinburgh: Academic Press, 2002.

ALTER, B. P. et al. Fanconi anemia: myelodysplasia as a predictor of outcome. Cancer Genet Cytogenet, New York, v. 17, p. 125–131, 2000. DOI: https://doi.org/10.1016/s0165-4608(99)00159-4. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0165460899001594. Acesso em: 9 jan. 2020.

BALKAN, M. et al. Cytogenetic analysis of 4216 patients referred for suspected chromosomal abnormalities in Southeast Turkey. Genet Mol Res, Ribeirão Preto, v, 9, n. 2, p. 1094-103, 2010. DOI: https://doi.org/10.4238/vol9-2gmr827. Disponível em: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.603.9118&rep=rep1&type=pdf. Acesso em: 20 jan. 2020.

BIESECKER, L. G.; SPINNER, N. B. A genomic view of mosaicism and human disease. Nat Rev Genet, London, v. 14, n. 5, p. 307–20, 2013. DOI: https://doi.org/10.1038/nrg3424. Disponível em: https://www.nature.com/articles/nrg3424. Acesso em: 10 fev. 2020.

BONTHRON, D. T.; STRAIN L.; DEAN J. C. S. Amalgamation of in vitro fertilized embryos, resulting in birth of a true hermaphrodite chimera. Am J Hum Genet, Hampshire, v. 61, p. A147, 1997. Disponível em: https://scirp.org/reference/referencespapers.aspx?referenceid=362514. Acesso em: 4 jan. 2020.

BORNSTEIN, E. et al. Comparison of modes of ascertainment for mosaic vs complete trisomy 21. Am J Obstet Gynecol, New York, v. 200, p. 440.e1–e5, 2009. DOI: https://doi.org/10.1016/j.ajog.2009.01.017. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0002937809000994. Acesso em: 3 jan. 2020.

CONLIN, L. K. et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified bysingle nucleotide polymorphism array analysis. Hum. Mol. Genet, New York, v. 19, p. 1263–1275, 2010. DOI: https://doi.org/10.1093/hmg/ddq003. Disponível em: https://academic.oup.com/hmg/article/19/7/1263/2901116. Acesso em: 4 jan. 2020.

DE LA CHAPELLE, A. The etiology of maleness in XX men. Hum Genet, Berlin, v. 58, n. 1, p. 105-16, 1981. DOI: 10.1007/BF00284157. Disponível em: https://link.springer.com/content/pdf/10.1007/BF00284157.pdf. Acesso em: 5 dez. 2019.

DUARTE, A. C. et al. Cytogenetics of genetic counseling patients in Pelotas, Rio Grande do Sul, Brazil. Genet Mol Res, Ribeirão Preto, v. 3, n. 3, p. 303-308, 2008. Disponível em: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.498.7712&rep=rep1&type=pdf. Acesso em: 25 jan. 2020.

FAGERBERG, C. R. et al. Trisomy 14 mosaicism: clinical and cytogenetic findings in an adult. Clinical dysmorphology, London, v. 21, n. 1, p. 45-47, 2012. DOI: https://doi.org/10.1097/MCD.0b013e32834a0436. Disponível em: https://journals.lww.com/clindysmorphol/Fulltext/2012/01000/Trisomy_14_mosaicism_clinical_and_cytogenetic.12.aspx. Acesso em: 22 jan. 2020.

FEUK, L.; CARSON, A. R.; SCHERER, S. W. Structural variation in the human genome. Nature Rev Genet, London, v. 7, p. 85-97, 2006. Disponível em: https://www.nature.com/articles/nrg1767. Acesso em: 2 abr. 2020.

FUJIMOTO, A. et al. Natural history of mosaic trisomy 14 syndrome. American journal of medical genetics, New York, v. 44, n. 2, p. 189-196, 1992. DOI: https://doi.org/10.1002/ajmg.1320440214. Disponível em: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.1320440214. Acesso em: 3 fev. 2020.

GARDNER, R. J. M; SUTHERLAND, G.R.; SHAFFER, L. G. Chromosome abnormalities and genetic counseling. 4th. ed. Oxford University Press: Oxford, 2012.

GERSAK, K.; VEBLE, A. Low-level X chromosome mosaicism in women with sporadic premature ovarian failure. Reproductive biomedicine online, Amsterdam, v. 22, n. 4, p. 399-403, 2011. DOI: https://doi.org/10.1016/j.rbmo.2011.01.002. Disponível em: https://www.sciencedirect.com/science/article/pii/S1472648311000125. Acesso em: 5 fev. 2020.

GERSEN, S. L.; KEAGLE, M. B. The principles of clinical cytogenetics. 2nd. ed. New Jersey: Humana Press, 2004.

GOSWAMI, D.; CONWAY, G. S. Premature ovarian failure. Hum. Reprod, Oxford, v. 11, p. 391–410, 2005. DOI: https://doi.org/10.1093/humupd/dmi012. Disponível em: https://academic.oup.com/humupd/article-abstract/11/4/391/874983. Acesso em: 18 fev. 2020.

HASSOLD, T.; HUNT, P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet, London, v. 2, p. 280-291, 2001. Disponível em: https://www.nature.com/articles/35066065. Acesso em: 4 fev. 2020.

HOULIHAN O. A., O’DONOGHUE K. The natural history of pregnancies with a diagnosis of trisomy 18 or trisomy 13; a retrospective case series. BMC Pregnancy Childbirth, London, v. 13, p. 209, 2013. DOI: https://doi.org/10.1186/1471-2393-13-209. Disponível em: https://link.springer.com/article/10.1186/1471-2393-13-209. Acesso em: 4 fev. 2020.

ISCN. International Standing Committee on Human Cytogenomic Nomenclature. ISCN: an international system for human cytogenomic nomenclature (2016). Karger: New York, 2016.

JACKSON-COOK, C. Constitutional and acquired autosomal aneuploidy. Clin Lab Med, Philadelphia, v. 31, p. 481–511, 2011. DOI: https://doi.org/10.1016/j.cll.2011.08.002. Disponível em: https://www.labmed.theclinics.com/article/S0272-2712(11)00068-0/abstract. Acesso em: 1 jan. 2020.

JUNG, M. P. et al. Diagnóstico da Síndrome de Turner: a experiência do Instituto Estadual de Diabetes e Endocrinologia - Rio de Janeiro, de 1970 a 2008. Revista Brasileira de Saúde Materno Infantil, Recife, v. 10, n. 1, p. 117-124, 2010. DOI: https://doi.org/10.1590/S1519-38292010000100012. Disponível em: https://www.scielo.br/scielo.php?script=sci_arttext&pid=S1519-38292010000100012&lang=pt. Acesso em 21 fev. 2020.

KIM, J.W. et al. SRY-negative 46,XX infertile male with Leydig cell hyperplasia: clinical, cytogenetic, and molecular analysis and review of the literature. Fertil Steril, New York, v. 94, n. 2: p. 753.e5-9, 2010. DOI: https://doi.org/10.1016/j.fertnstert.2010.01.050. Disponível em: https://www.sciencedirect.com/science/article/pii/S0015028210001251. Acesso em: 1 jan. 2020.

LAKHAL, B. et al. Cytogenetic analyses of premature ovarian failure using karyotyping and interphase fluorescence in situ hybridization (FISH) in a group of 1000 patients. Clin. Genet, Copenhagen, v. 78, p. 181–185, 2010. DOI: https://doi.org/10.1111/j.1399-0004.2009.01359.x. Disponível em: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-0004.2009.01359.x. Acesso em: 19 fev. 2020.

LY, D.H. et al. Mitotic misregulation and human aging. Science, New York, v. 287, p. 2486–2492, 2000. DOI: https://doi.org/10.1126/science.287.5462.2486. Disponível em: https://science.sciencemag.org/content/287/5462/2486.abstract. Acesso em: 3 fev. 2020.

MAU, U.A. et al. Chromosomal findings in 150 couples referred for genetic couselling prior to intracytoplasmic sperm injection. Hum Reprod, Oxford, v. 12, p. 930–937, 1997. DOI: https://doi.org/10.1093/humrep/12.5.930. Disponível em: https://academic.oup.com/humrep/article-abstract/12/5/930/665457. Acesso em: 3 fev. 2020.

MESCHEDE, D. et al. Chromosome abnormalities in 447 couples undergoing intracytoplasmic sperm injection prevalence, types, sex distribution and reproductive relevance. Hum Reprod, Oxford, v. 13, p. 576–582, 1998. DOI: https://doi.org/10.1093/humrep/13.3.576. Disponível em: https://academic.oup.com/humrep/article-abstract/13/3/576/733528. Acesso em: 3 fev. 2020.

PAPAVASSILIOU, P. et al. The phenotype of persons having mosaicism for trisomy 21/Down syndrome reflects the percentage of trisomic cells present in different tissues. Am J Med Genet Part A, Hoboken, v. 149A, p. 573-583, 2009. DOI: https://doi.org/10.1002/ajmg.a.32729. Disponível em: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajmg.a.32729. Acesso em: 2 fev. 2020.

RODRIGUES, M. A. et al. Low-level trisomy 14 mosaicism in a male newborn with ectrodactyly. Genet Mol Res, v. 15, p. 1-7, 2016.

RODRIGUES, M. A. et al. Mosaic 15q duplication syndrome (tetrasomy 15q11. 1-q13. 2) in a child with behavior disorders: case report. Brazilian Journal of Psychiatry, v. 41, n. 1, p. 93-95, 2019.

RUSSELL, L.M. et al. X chromosome loss and ageing. Cytogenet. Genome. Res, Basel, v. 116, p. 181–185, 2007. DOI: https://doi.org/10.1159/000098184. Disponível em: https://www.karger.com/Article/Abstract/98184. Acesso em: 3 fev. 2020.

SHARP, A.J.; CHENG, Z.; EICHLER, E.E. Structural variation of the human genome. Annu Rev Genomics Hum Genet, London, v. 7, p. 407–442, 2006. Disponível em: https://www.nature.com/articles/nrg1767. Acesso em: 3 fev. 2020.

SHIN, M.; SIFFEL, C.; CORREA, A. Survival of children with mosaic Down syndrome. Am J Med Genet Part A, Hoboken, v. 152A, p. 800–801, 2010. DOI: https://doi.org/10.1002/ajmg.a.33295. Disponível em: https://www.academia.edu/download/47586268/ajmg.a.3329520160728-27005-w4ubto.pdf. Acesso em: 3 fev. 2020.

SIMPSON, J. L. Genetic and phenotypic heterogeneity in ovarian failure: overview of selected candidate genes. Ann. N. Y. Acad. Sci, New York, v. 11, p. 146–154, 2008. DOI: https://doi.org/10.1196/annals.1429.019. Disponível em: https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1429.019. Acesso em: 3 fev. 2020.

SONNTAG, B. et al. Low-level sex chromosome mosaicism in female partners of couples undergoing ICSI therapy does not significantly affect treatment outcome. Hum Reprod, Oxford, v. 16, p. 1648–1652, 2001. DOI: https://doi.org/10.1093/humrep/16.8.1648. Disponível em: https://academic.oup.com/humrep/article-abstract/16/8/1648/624671. Acesso em: 3 fev. 2020.

SOYLEMEZ, F. Double Aneuploidy in Down Syndrome, Health Problems in Down Syndrome. London: IntechOpen, 2015. E-book. Disponível em: https://www.intechopen.com/books/health-problems-in-down-syndrome/double-aneuploidy-in-down-syndrome. Acesso em: 10 dez. 2019.

UEHARA, S. et al. Molecular biologic analyses of tetragametic chimerism in a true hermaphrodite with 46,XX/46,XY. Fertil Steril, New York, v. 63, p. 189–192, 1995. DOI: https://doi.org/10.1016/s0015-0282(16)57317-8. Disponível em: https://pubmed.ncbi.nlm.nih.gov/7805911/. Acesso em: 20 fev. 2020.

VAN DOOREN, M.F.; BERTOLI-AVELLAB, A.M.; OLDENBURG, R.A. Premature ovarian failure and gene polymorphisms. Curr. Opin. Obstet. Gynecol, Philadelphia, v. 21, p. 313–317, 2009. DOI: https://doi.org/10.1097/GCO.0b013e32832e0813. Disponível em: https://cdn.journals.lww.com/co-obgyn/Fulltext/2009/08000/Premature_ovarian_failure_and_gene_polymorphisms.5.aspx. Acesso em: 3 fev. 2020.

WISE, J. L. et al. Cryptic subtelomeric rearrangements and X chromosome mosaicism: a study of 565 apparently normal individuals with fluorescent in situ hybridization. PLoS. One, San Francisco, v. 10, e5855, 2009. DOI: https://doi.org/10.1371/journal.pone.0005855. Disponível em: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005855. Acesso em: 3 fev. 2020.

WONG, M.S.; LAM, S.T. Cytogenetic analysis of patients with primary and secondary amenorrhoea in Hong Kong: retrospective study. Hong Kong Med, Hong Kong, J. v. 11, p. 267–672, 2005. Disponível em: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.507.4647&rep=rep1&type=pdf. Acesso em: 3 fev. 2020.

YU, N. et al. Disputed maternity leading to identification of tetragametic chimerism. N Engl J Med, Boston, v. 346, p. 1545–1552, 2002. DOI: https://doi.org/10.1056/NEJMoa013452. Disponível em: https://www.nejm.org/doi/full/10.1056/nejmoa013452. Acesso em: 3 fev. 2020.

ZARAGOZA, M. et al. Nondisjunction of human acrocentric chromosomes: studies of 432 fetuses and liveborns. Hum. Genet, Berlin, v. 94, p. 411–417, 1994. DOI: https://doi.org/10.1007/BF00201603. Disponível em: https://link.springer.com/content/pdf/10.1007/BF00201603.pdf. Acesso em: 3 fev. 2020.