Abstract
Chromosomal aberrations such as parental balanced translocation contribute to a significant proportion of recurrent pregnancy losses. These have extreme genetic implications on the foetus which can either cause physical and/or mental retardation or early death. In this study, we report a unique clinical case of a couple with three consecutive pregnancy losses and we aim to determine the genetic abnormalities causing the miscarriages. Conventional cytogenetic and molecular genetic analysis were performed on the products of conception as well as for the parents. Chromosomal analysis was performed based on the ISCN 2016 guidelines. This was followed by Chromosomal microarray analysis carried out using ISCA consortium probe set (8X60K). Genetic testing for the 1st product of conception was not performed. However, the 2nd and 3rd products of conception indicated an autosomal trisomy 22 and a 3.7 Mb deletion of 2p (cytoband p25.3) along with 13.6 Mb duplication of 16p (cytoband p13.3p13.12), respectively. The paternal karyotype was normal but mother showed a balanced translocation 46,XX,t(2;16)(p25.3;p13.3). This was parallel to the products of conception microarray findings, unbalanced chromosomal abnormality in the foetus. Balanced translocation carriers are susceptible for meiotic nondisjunction processes and early detection of genetic anomalies can be informative to parents trying to conceive. Genetic analysis of the abortus after the 1st loss can be helpful to understand the cause of miscarriage. A combined approach with microarray and karyotyping of the products of conception can be important to determine the specific aberrations in the foetal chromosomes leading to abortion.
This is a preview of subscription content, log in via an institution to check access.
References
Choi T. Y., Lee H. M., Park W. K., Jeong S. Y. and Moon H. S. 2014 Spontaneous abortion and recurrent miscarriage: a comparison of cytogenetic diagnosis in 250 cases. Obstet. Gynecol. Sci. 57, 518–525.
De P., Chakravarty S. and Chakravarty A. 2015 Novel balanced chromosomal translocations in females with recurrent spontaneous abortions: two case studies. J. Hum. Reprod. Sci. 8, 114–117.
Digilio M. C., Bernardini L., Capalbo A., Capolino R., Gagliardi M. G., Marino B. et al. 2009 16p subtelomeric duplication: a clinically recognizable syndrome. Eur. J. Med. Genet. 17, 1135–1140.
Flynn H., Yan J., Saravelos S. H. and Li T. C. 2014 Comparison of reproductive outcome, including the pattern of loss, between couples with chromosomal abnormalities and those with unexplained repeated miscarriages. J. Obstet. Gynaecol. Res. 40, 109–116.
Gardner R. J. M., Sutherland G. R. and Shaffer L. G. 2012 Chromosome abnormalities and genetic counseling, 4th edition. Oxford University Press, Oxford, UK.
Ghazaey S., Keify F., Mirzaei F., Maleki M., Tootian S., Ahadian M. and Abbaszadegan M. R. 2015 Chromosomal analysis of couples with repeated spontaneous abortions in Northeastern Iran. Int. J. Fertil. Steril. 9, 47–54.
Jobanputra V., Sobrino A., Kinney A., Kline J. and Warburton D. 2002 Multiplex interphase fish as a screen for common aneuploidies in spontaneous abortions. Hum. Reprod. 17, 1166–1170.
Kunwar F. and Bakshi S. R. 2016 Familial constitutional rearrangement of chromosomes 4 & 8: phenotypically normal mother and abnormal progeny. J. Clin. Diagn. Res. 10, Gd01–Gd04.
Levy B., Sigurjonsson S., Pettersen B., Maisenbacher M. K., Hall M. P., Demko Z. et al. 2014 Genomic imbalance in products of conception: single-nucleotide polymorphism chromosomal microarray analysis. Obstet. Gynecol. 124, 202–209.
Mackie Ogilvie C. and Scriven P. N. 2004 Preimplantation genetic diagnosis (PGD) for reciprocal translocations. Prenat. Diagn. 24, 553–555.
Pourjafari B., Pour-Jafari H., Farimani M., Ghahramani S. and Saleh E. K. 2012 Genetic counseling in carriers of reciprocal translocations involving two autosomes. Indian J. Hum. Genet. 18, 250–253.
Pylyp L. Y., Spynenko L. O., Verhoglyad N. V., Mishenko A. O., Mykytenko D. O. and Zukin V. D. 2018 Chromosomal abnormalities in products of conception of first-trimester miscarriages detected by conventional cytogenetic analysis: a review of 1000 cases. J. Assist. Reprod. Genet. 35, 265–271.
Sadler T. W. and Langman J. 2011 Langman’s medical embryology, 12th edition. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia.
Sheth F. J., Liehr T., Kumari P., Akinde R., Sheth H. J. and Sheth J. J. 2013 Chromosomal abnormalities in couples with repeated fetal loss: an Indian retrospective study. Indian J. Hum. Genet. 19, 415–422.
Sierra S. and Stephenson M. 2006 Genetics of recurrent pregnancy loss. Semin. Reprod. Med. 24, 17–24.
Stern C., Pertile M., Norris H., Hale L. and Baker H. 1999 Chromosome translocations in couples with in-vitro fertilization implantation failure. Hum. Reprod. 14, 2097–2101.
van den Berg M. M., van Maarle M. C., van Wely M. and Goddijn M. 2012 Genetics of early miscarriage. Biochim. Biophys. Acta Mol. Basis Dis. 1822, 1951–1959.
Zhu X., Li J., Zhu Y., Wang W., Wu X., Yang Y., Gu L. et al. 2018 Application of chromosomal microarray analysis in products of miscarriage. Mol. Cytogenet. 11, 44.
Acknowledgements
Authors acknowledge support from Advanced Genomics Institute and Laboratory Medicine, AGILE, New Delhi. Authors are grateful to the patients for the kind support and consent for the study.
Author information
Authors and Affiliations
Corresponding author
Additional information
Corresponding editor: B. K. Thelma
Rights and permissions
About this article
Cite this article
Shrivastava, A., Thakur, S., Nath, T. et al. Parental balanced chromosomal rearrangement leading to major genomic imbalance and an autosomal trisomy resulting in consecutive pregnancy loss: a case report. J Genet 100, 54 (2021). https://doi.org/10.1007/s12041-021-01304-3
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12041-021-01304-3