Higher CNV Frequencies in Chromosome 14 of Girls With Turner Syndrome Phenotype

Context: Precise genotype-phenotype correlations in Turner syndrome (TS) have not yet been deciphered. The chromosomal basis of the clinical TS phenotype in the absence of X chromosome aberrations on conventional karyotyping remains more and less unexplored.

Objective: To elucidate the high-resolution chromosomal picture and analyze the genotype-phenotype associations in girls with clinical phenotype of TS by chromosomal microarray.

Design and patients: Cross sectional observational study conducted between October 2018 and January 2020 on 47 girls presenting the clinical TS phenotype and fulfilling the criteria for chromosomal analysis.

Setting: Outpatient department at Department of Endocrinology and the Molecular Research Lab at tertiary care teaching institution.

Results: The copy number variation (CNV) polymorphs were more frequent on autosomes than X chromosomes, and they were detected in 89.3%, 61.7%, and 92.8% of patients, respectively, on chromosome 14 or X or both. A total 445 and 64 CNV polymorphs were discovered on chromosome X and 14, respectively. The latter exhibited either gain at 14q32.33, loss at 14q11.2, or both. Karyotype was available for 27 patients; 55.6% of cases displayed X chromosome abnormalities while 44.4% cases had a normal karyotype. Functional interactomes of the genes that were present in chromosome 14 CNVs and those known to be associated with TS showed an overlap of 67% and enriched various development-related cellular pathways underlying TS phenotype.

Conclusions: On high-resolution karyotype analysis, clinical phenotype of TS can be associated with CNV defects in autosomes, specifically chromosome 14 or X chromosome or both. The syndrome of chromosome 14 CNV defects with and without X-chromosomal defects clinically mimics TS and shares a common genomic network that deserves further investigations.