Higher CNV frequencies in Chromsome-14 of girls with Turner syndrome phenotype - A chromosomal microarray study.

Abstract

CONTEXT\nPrecise 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 the conventional karyotyping remains more and less unexplored.\n\n\nOBJECTIVE\nTo elucidate the high resolution chromosomal picture and analyze the genotype -phenotype associations in girls with clinical phenotype of TS by chromosomal microarray (CMA).Design and Patients: Cross sectional observational study conducted between October 2018 to January 2020 on 47 girls presenting the clinical TS-phenotype and fulfilling the criteria for chromosomal analysis.\n\n\nSETTING\nOut Patient Department at Department of Endocrinology and the Molecular research lab at tertiary care teaching institution.\n\n\nRESULTS\nThe CNV (copy number variation) 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. Total 445 and 64 CNV polymorphs were discovered on chromosome X and 14 respectively. The latter exhibiting either gain at 14q32.33 or loss at 14q11.2 or both. Karyotype was available for 27 patients; 55.6% cases displayed X chromosome abnormalities while 44.4% cases had a normal karyotype. Functional interactomes of the genes those 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.\n\n\nCONCLUSIONS\nOn high resolution karyotype analysis, clinical phenotype of TS could be found associated with CNV defects in autosomes (specifically Chr. 14,) or X chromosome or both. The syndrome of chromosome 14 CNVs defects with and without X-chromosomal defects clinically mimics TS and shares a common genomic network deserves further investigations.