Mosaicism For Autosomal Trisomies: A Review of The Literature Suggests Inverse Effects of Carriers’ Gender and Maternal Age on Clinical Manifestations

Author(s): Natalia V. Kovaleva, Philip D. Cotter

Various clinical aspects of human mosaicism have been thoroughly investigated worldwide for some time. Female predominance among mosaic carriers was reported, but the clinical significance of mosaic carriers’ gender was not evaluated. The current study is the first to consider the diverse aspects of male-to-female ratio (sex ratio, SR) variations in somatic diploid/trisomic mosaicism. The data on gender and clinical status of mosaic carriers and maternal age were retrieved for 948 prenatal diagnoses including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). Remarkably, the overall SRs in every study cohort were female-biased, being 0.8 each. However, mosaic trisomies for chromosomes 7, 8, 10, and 20 demonstrated a male prevalence across TFM, CPM and PNM cohorts, unlike to mosaic trisomies 9, 12, 13. 14, 18, 21, and 22 with a female prevalence. We found an apparent predominance of females among abnormal outcomes; 49 males and 73 females (SR=0.67) vs normal 45 males and 41 females (SR=1.1). Further analysis determined a sex-specific negative effect of certain chromosomes involved including chromosomes 2 (male-specific), 4, 9, 11, 12, 18, and 22 (female-specific). Female predominance was observed in cases of intrauterine fetal losses and in cases of intrauterine growth restriction. A higher proportion of advanced maternal age was found in normal outcomes, either male or female mosaic carriers in every studied cohort demonstrating a “positive” effect, opposite to “negative” effect of female gender. The data reported requires further strengthening by collective international efforts.