Detection of Germline Mosaicism for Robertsonian Translocation 14;14:  A Case Report

Xavier Viñals  Gonzalez; Francisca  Mora; Falak  Arshad; Yiping  Zhang; Dhruti  Babariya; Dagan  Wells; Amanda Tozer

doi:10.18502/jri.v25i1.15202

Xavier Viñals Gonzalez Embryology Department, Aria Fertility, London, UK
Francisca Mora Embryology Department, Aria Fertility, London, UK
Falak Arshad Reproductive Genetics Department, Juno Genetics, Oxford, UK
Yiping Zhang Reproductive Genetics Department, Juno Genetics, Oxford, UK
Dhruti Babariya Reproductive Genetics Department, Juno Genetics, Oxford, UK
Dagan Wells Reproductive Genetics Department, Juno Genetics, Oxford, UK
Amanda Tozer Clinical Department, Aria Fertility, London, UK

DOI: https://doi.org/10.18502/jri.v25i1.15202

Keywords: In vitro fertilization, Miscarriage, Mosaicism.

Abstract

Background: Chromosomal structural rearrangements can lead to fertility problems and recurrent miscarriages. The intricate interplay of genetics during human development can lead to subtle anomalies that may affect reproduction.

Case Presentation: A 33-year-old woman sought fertility treatment after experiencing six miscarriages. Products of conception from the final pregnancy loss had been karyotyped, revealing a Robertsonian translocation (RT), involving chromosome 14. Fertility investigations showed low anti-Mullerian hormone (AMH) levels but otherwise normal female characteristics with normal sperm parameters of her husband were observed and both partners having a normal karyotype. Two embryos were transferred in an IVF cycle but neither resulted in a successful pregnancy. Subsequently, preimplantation genetic testing for aneuploidy (PGT-A) was applied to trophectoderm biopsy specimens from 4 embryos, which revealed abnormalities involving chromosome 14. Sperm aneuploidy testing failed to detect any increase in the incidence of aneuploidy affecting chromosome 14. Further embryos genetic testing indicated that all identified chromosome 14 abnormalities in the embryos had a maternal (oocyte) origin.

Conclusion: This case underscores challenges in diagnosing and managing germline mosaicism in fertility. A maternal 14;14 Robertsonian translocation, undetected in the patient's blood but impacting oocytes, likely explains recurrent miscarriage and observed embryo aneuploidies. Genetic mosaicism in reproductive medicine highlights the necessity for advanced testing and personalized treatments. Data integration from various genetic analyses could enhance managing treatment expectations and improving fertility experiences.