Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

An Incidental Detection of a Cryptic Complex Chromosome Rearrangement Found During NGS Based PGT-SR: A Case Report

Authors
Leyla Özer 1
Suleyman Aktuna 1
Evrim Unsal 1
Aysun Baltaci 2
Volkan Baltaci 1
1 Department of Medical Genetics, Faculty of Medicine, Yuksek İhtisas University, Ankara, Turkey; Mikrogen Genetic Diagnosis Center, Ankara, Turkey
2 Gen-Art IVF Center, Ankara, Turkey
10.18502/jri.v23i4.10817
Abstract
Background: Complex chromosome rearrangements (CCRs) involve more than 2 chromosomal breakpoints and cause the exchanges of chromosomal segments between two or more chromosomes. The carriers of CCRs have normal phenotypes, but they have a higher risk of reproductive failure. Case Presentation: This paper presents a couple with a history of two affected children, one spontaneous abortion, three in vitro fertilization (IVF) failures, and one healthy boy who were referred to our laboratory for preimplantation genetic testing (PGT). The wife had been evaluated as a carrier of 46,XX,t (2;6)(p21;p25); therefore, four IVF treatment cycles supported with PGT for this translocation had been performed in different IVF centers until the couple consulted our laboratory. Only one of these four IVF attempts had resulted in a healthy boy and this IVF study had been performed with fluorescence in situ hybridization (FISH)-based preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR). The fifth IVF study with next-generation sequencing (NGS)-based PGT was performed by our laboratory and no healthy embryo was found in evaluated 6 embryos. During our NGS-based PGT, the cryptic involvement of 12p was firstly detected. FISH with chromosome 2,6, and 12 specific probes revealed that the mother was a carrier of a balanced 3-way translocation of 46,XX,t(2;6;12)(p21;p25;p13). Conclusion: NGS based PGT-SR method is an accurate method for detecting the copy number variations and is helpful to find out the cryptic CCRs.
Keywords
Chromosomal abnormalities
Chromosomal translocation
next generation sequencing
Preimplantation genetic testing
Pellestor F, Anahory T, Lefort G, Puechberty J, Liehr T, He´don B, et al. Complex chromosomal rearrangements: origin and meiotic behavior. Hum Reprod Update. 2011;17(4):476-94.
Madan K. Balanced complex chromosome rearrangements: reproductive aspects. a review. Am J Med Genet Part A. 2012;158A(4):947-63.
Madan K. What is a complex chromosome rearrangement? Am J Med Genet A. 2013;161A(5):1181-4.
Gorski JL, Kistenmacher ML, Punnett HH, Zackai EH, Emanuel BS. Reproductive risks for carriers of complex chromosome rearrangements: analysis of 25 families. Am J Med Genet. 1988;29(2):247-61.
Madan K, Nieuwint AW, Van Bever Y. Recombination in a balanced complex translocation of a mother leading to a balanced reciprocal translocation in the child. Review of 60 Cases of balanced complex translocations. Hum Genet. 1997;99(6):806-15.
Hu L, Wei Y, Luo K, Xie P, Gong F, Xiong B, et al. Clinical outcomes in carriers of complex chromosomal rearrangements: a retrospective analysis of comprehensive chromosome screening results in seven cases. Fertil Steril. 2018;109(3):486-92.
Scriven PN, Bint SM, Davies AF, Ogilvie CM. Meiotic outcomes of three-way translocations ascertained in cleavage-stage embryos: refinement of reproductive risks and implications for PGD. Eur J Hum Genet. 2014;22(6):748-53.
Harton G, Braude P, Lashwood A, Schmutzler A, Traeger-Synodinos J, Wilton L, et al. ESHRE PGD consortium best practice guidelines for organization of a PGD centre for PGD/preimplantation genetic screening. Hum Reprod. 2010;26(1):14-24.
ESHRE PGT consortium steering committee, Carvalho F, Coonen E, Goossens V, Kokkali G, Rubio C, et al. ESHRE PGT consortium good practice recommendations for the organisation of PGT. Hum Reprod Open. 2020;2020(3):hoaa021.
[No Authors listed]. Preimplantation genetic testing: ACOG committee opinion, Number 799. Obstet Gynecol. 2020;135(3):e133-e7.
Gregori MD, Ciccone R, Magini P, Pramparo T, Gimelli S, Messa J, et al. Cryptic deletions are a common finding in "balanced" reciprocal and complex chromosome rearrangements: A study of 59 patients. J Med Genet. 2007;44(12):750-62.
Escudero T, Estop A, Fischer J, Munne S. Preimplantation genetic diagnosis for complex chromosome rearrangements. Am J Med Genet A. 2008;146A(13):1662-9.
Vanneste E, Melotte C, Voet T, Robberecht C, Debrock S, Pexsters A, et al. PGD for a complex chromosomal rearrangement by array comparative genomic hybridization. Hum Reprod. 2011;26(4):941-9.
Nonaka T, Ooki I, Enomoto T, Takakuwa K. Complex chromosomal rearrangements in couples affected by recurrent spontaneous abortion. Int J Gynaecol Obstet. 2015;128(1):36-9.
Li G, Shi W, Niu W, Xu J, Guo Y, Su Y, et al. The influence of balanced complex chromosomal rearrangements on preimplantation embryonic development potential and molecular karyotype. BMC Genomics. 2020;21(1):326.
Athalye A, Sanap R, Madon P, Naik D, Warang D, Padyal P, et al. Preimplantation genetic testing for a complex chromosome rearrangement, case report of a cryptic translocation detected on pre-PGT workup. Obstet Gynecol Int J. 2018;9(2):138-41.
McKenzie LJ, Cisneros PL, Torsky S, Bacino CA, Buster JE, Carson SA, et al. Preimplantation genetic diagnosis for a known cryptic translocation: follow-Up clinical report and implication of segregation products. Am J Med Genet. 2003;121A(1):56-9.
Brunet B, Shen J, Cai L, Xie J, Cui Y, Liu J, et al. Preimplantation genetic testing for complex chromosomal rearrangement carriers by next-generation sequencing. Reprod Biomed Online. 2018;37(3):375-82.
Wang X, Wu C, Hao D, Zhang J, Tan C, Cheng D, et al. One healthy live birth after preimplantation genetic testing of a cryptic balanced translocation (9;13) in a family with cerebral palsy and glaucoma: a case report. BMC Med Genomics. 2021;14(1):82.
Frumkin T, Peleg S, Gold V, Reches A, Asaf S, Azem F, et al. Complex chromosomal rearrangement-a lesson learned from PGS. J Assist Reprod Genet. 2017;34(8):1095-1100.
Journal of Reproduction & Infertility
Volume 23, Issue 4
Autumn 2022
Pages 303-309