Optical genome mapping resolves a complex dicentric X chromosome involving the XIST region in Turner syndrome: a case report

Abstract Background Turner syndrome (TS) is a common sex chromosome aneuploidy characterized by significant phenotypic variability, partly influenced by mosaicism and structural abnormalities of the X chromosome. Alterations involving the X-inactivation center, particularly the XIST locus, have been associated with neurodevelopmental outcomes. However, the impact of XIST copy number gains remains poorly understood. Case presentation We report a prenatally diagnosed case of atypical TS with mosaic 45,X/46,X, der(X) karyotype. Prenatal analyses identified a structurally abnormal X chromosome with a complex mosaic copy-number profile involving the XIST-containing region. Conventional cytogenetic techniques confirmed mosaicism but did not fully resolve the chromosomal architecture. OGM enabled high-resolution characterization of the complex derivative X chromosome, revealing an inversion and an inverted duplication involving the XIST-containing region. Variant allele frequency patterns supported a complex multistep rearrangement contributing to the derivative chromosome. At 8 years of age, the patient exhibited typical Turner features, including short stature requiring growth hormone therapy, but normal intellectual functioning with no global developmental delay. Conclusion This case highlights the added value of OGM in resolving complex X-chromosome rearrangements in TS. Despite the complex rearrangement and multiple copies of the XIST-containing region, the patient showed no global developmental delay or intellectual disability at 8 years of age. Whether preservation of the XIST-containing region contributes to this relatively favorable neurodevelopmental outcome remains hypothetical and requires functional investigation.