Evidence for the Oocyte Mosaicism Selection model on the origin of Patau syndrome (trisomy 13)

Abstract

Introduction In 2008, Hultén et al hypothesized that maternal ovarian trisomy 21 mosaicism might be the primary causative factor for fetal Down syndrome. We hypothesize that this theory can be extended to trisomy 13. Material and methods We collected fetal ovarian tissue from seven female fetuses between 16 and 23 gestational weeks, following the termination of the pregnancy for non‐genetic reasons. All procedures were performed with informed consent and ethical approval from the local ethics committee. We used touch preparation techniques from fetal ovarian tissues and an anti‐stromal antigen 3 antibody against the meiosis‐specific stromal antigen 3 protein to differentiate between germ cells, ovarian stromal cells and the cells entering their first meiotic prophase. We used fluorescence in situ hybridization analysis to determine chromosome 13 numbers in each cell. Results We were able to detect a proportion of trisomy 13 cells in all cases. The average incidence of trisomy 13 cells was 2.04% in stromal antigen 3‐positive and 0.91% in the stromal antigen 3‐negative cells. The number of the trisomic cells increased significantly with gestational age (for stromal antigen 3‐positive cells r = 0.93, P = 0.0038, for stromal antigen 3‐negative cells r = 0.85, P = 0.0071). Conclusions This study indicates that besides trisomy 21, the Oocyte Mosaicism Selection model could be extended to trisomy 13 as well. The crucial factor for trisomy 13 seems to be the pre‐meiotic/mitotic trisomy 13 mosaicism, leading to a so‐called secondary meiotic nondisjunction of those oocytes having three copies of chromosome 13.

Review of epidemiological factors (other than maternal age) that determine the prevalence of common autosomal trisomies

“…35,36 In another study, seven ovarian tissue samples were analyzed to look for trisomy 13 mosaicism and evidence was found in all cases. 37 However, using the same FISH method, other researchers found virtually none in eight first 38 and 7 second trimester fetuses. 39 Applying FISH to a large number of sperm cells from eight men the incidence of disomy 21 was over 0.1%.…”

“…Using fluorescence in situ hybridization (FISH) with two probes, one investigator found trisomy 21 in almost 0.1% of cells from 12 first trimester fetuses and over 0.5% in 8 second trimester fetuses 35,36 . In another study, seven ovarian tissue samples were analyzed to look for trisomy 13 mosaicism and evidence was found in all cases 37 . However, using the same FISH method, other researchers found virtually none in eight first 38 and 7 second trimester fetuses 39 .…”