Origin of trisomy: no evidence to support the ovarian mosaicism theory

Trisomy is the most common type of chromosome abnormality, affecting 4% of clinically recognised pregnancies, of which, trisomies 16, 21 and 22 are the most prevalent. It has been suggested that a large proportion of maternally derived trisomic pregnancies, specifically trisomy 21, are the result of low-level ovarian mosaicism. In this study, we aimed to reproduce these previously published results on trisomy 21 and investigate the other common maternally derived trisomies (i.e. trisomies 16 and 22) by determining chromosome copy number in fetal ovarian and control skin cells.

Ovarian and control skin tissue was collected from eight karyotypically normal female fetuses of between 10 and 14 weeks gestation, which were terminated for social reasons. Tissues were dissociated and fluorescence in situ hybridisation was performed with break-apart probes: CBFβ (16q22), RUNX1 (21q22) and EWSR1 (22q12).

A small number of trisomic cells, 13 out of 51,146 cells examined (0.025%), were identified in both ovarian and control skin samples. Only three of these trisomic cells were present in the fetal ovarian tissue.

This study found no evidence of fetal ovarian mosaicism for trisomies 16, 21 and 22.