Background: Turner syndrome (TS) is caused by a total or partial loss of one X chromosome. Typical features include short stature and primary amenorrhoea. In addition, decreasing trabecular bone mineral density (BMD) and increasing cortical BMD during puberty has been reported at the radius. As chromosomal aberration remains a probable cause of bone changes in TS, we aimed to elucidate whether the karyotype differs among the tissues originating from the three different germ layers and whether this is associated with BMD.
Methods: Twenty-nine girls with TS aged 6.0-18.3 years (median: 11.8) participating in our previous bone density study (implementing peripheral quantitative CT at the radius) had new karyotyping. In addition to classical cytogenetic and molecular (fluorescence in situ hybridization, FISH) karyotyping from lymphocytes (mesoderm origin), FISH from cells gained through buccal (ectoderm origin) and root of tongue (endoderm origin) smears was also performed. Fifty (cytogenetic) and 250 (FISH) nuclei were analysed, respectively. SHOX gene deletion was considered "complete" whenever Xp was missing and "partial" in mosaicism. Percentage of X monosomy was calculated from the proportion of cell line with 45,X.
Results: There were 14 girls with mosaicism (5 with normal karyotype and 9 with aberrant second cell line) and 15 girls with 45,X karyotype in the lymphocytes as assessed by cytogenetics. "Complete" SHOX gene haploinsufficiency was present in 18 girls (either 45,X or Xp deletion in both cell lines), whereas in 6 girls, the Xp deletion was "partial" due to mosaicism. One subject presented 45,X monosomy in lymphocytes but had 45,X/47,XXX mosaicism in buccal and root of tongue cells. The maximum difference in percent X monosomy among the three germ layers was 15-66 (mean 37±18). Whereas trabecular volumetric BMD (vBMD) was not associated with percent X monosomy in either of the germ layers, cortical vBMD was negatively associated with percent X monosomy in the lymphocytes (β=-0.025±0.012, P=0.042 for cytogenetics and β=-0.028±0.013, P=0.048 for FISH) but not in buccal (β=-0.011±0.014, P=0.46) or root of the tongue cells (β=-0.013±0.012, P=0.32).
Conclusions: The karyotype result in TS differs by the embryonic origin of the tissue sample. Despite that the entire skeleton develops from mesoderm, only the cortical bone compartment had a quantitative association with X monosomy in lymphocytes. Gradual decrease in trabecular vBMD during puberty must have non-genetic causes. Knowledge of the karyotype of all three germ layers may help elucidate other features of TS.
Grant support (AZV 17-29111A )
19 - 21 Sep 2019
European Society for Paediatric Endocrinology