Turner's syndrome mosaicism in girls with neurodevelopmental disorders: a cohort study and hypothesis

Turner's syndrome is associated with either monosomy or a wide spectrum of structural rearrangements of chromosome X. Despite the interest in studying (somatic) chromosomal mosaicism, Turner's syndrome mosaicism (TSM) remains to be fully described. This is especially true for the analysis of TSM in clinical cohorts (e.g. cohorts of individuals with neurodevelopmental disorders). Here, we present the results of studying TSM in a large cohort of girls with neurodevelopmental disorders and a hypothesis highlighting the diagnostic and prognostic value.

Turner's syndrome-associated karyotypes were revealed in 111 (2.8%) of 4021 girls. Regular Turner's syndrome-associated karyotypes were detected in 35 girls (0.9%). TSM was uncovered in 76 girls (1.9%). TSM manifested as mosaic aneuploidy (45,X/46,XX; 45,X/47,XXX/46,XX; 45,X/47,XXX) affected 47 girls (1.2%). Supernumerary marker chromosomes derived from chromosome X have been identified in 11 girls with TSM (0.3%). Isochromosomes iX(q) was found in 12 cases (0.3%); one case was non-mosaic. TSM associated with ring chromosomes was revealed in 5 girls (0.1%).

The present cohort study provides data on the involvement of TSM in neurodevelopmental disorders among females. Thus, TSM may be an element of pathogenic cascades in brain diseases (i.e. neurodegenerative and psychiatric disorders). Our data allowed us to propose a hypothesis concerning ontogenetic variability of TSM levels. Accordingly, it appears that molecular cytogenetic monitoring of TSM, which is a likely risk factor/biomarker for adult-onset multifactorial diseases, is required.