Complex X-chromosome mosaicism with pronounced inter-tissue differences in a patient with secondary recurrent pregnancy loss

Abstract

Background. X-chromosome abnormalities are one of the common genetic causes of disorders of sex development, physical and sexual development, fertility. X-chromosome mosaicism in female patients can lead to various syndromic gonosomal abnormalities (Turner syndrome, trisomy X, and polysomy X, etc.), while similar karyotypes can occur in different clinical forms, this causes their partial overlap.

Aim: to present a clinical case of complex X-chromosome mosaicism in female patient with recurrent pregnancy loss. A 37-year-old woman applied for a genetic examination with complaints of miscarriage. The patient’s development was age-related. There are 3 natural pregnancies in the anamnesis, the first ended in the birth of a healthy boy, the second and the third were frozen in the early stages.

Methods. Standard cytogenetic study was performed on peripheral blood lymphocytes. Fluorescent in situ hybridization was performed on the nuclei of lymphocyte cells and buccal epithelial cells using centromeric probes for chromosomes 18 and X.

Results. The karyotype of the patient according to the standard cytogenetic study was determined as mos 45,X[29]/47,XXX[8]/46,XX[3]. FISH results shown complex X-chromosome mosaicism in peripheral blood lymphocytes – Х(78%)/ХХХ(10%)/ХХ(12%), and buccal epithelial cells – ХХХ(70%)/Х(7%)/ХХХХ(3%)/ХХ(20%).

Conclusion. Some female patients with complex X chromosome mosaicism may not have develop clinical signs characteristic of syndromic gonosomal abnormalities. Since these patients are at risk of premature ovarian insufficiency, they need a timely solution to the issue of reproduction with preimplantation genetic testing for aneuploidy (PGT-A) and prenatal cytogenetic diagnostics.