Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution

Abstract Individuals with Turner syndrome (TS) phenotypes may exhibit short stature, ovarian dysfunction, and neurocognitive disorders. Their genomes can include ring chromosomes formed from the X chromosome (RCX). Here, we present cytogenomic and clinical findings from seventeen individuals with TS...

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Main Authors: Anita Madison, Carolyn Applegate, Victoria Stinnett, Diego Marrero Miranda, Chantal Cross, Kamaria Cayton Vaught, Ying S. Zou, Jaclyn B. Murry
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-89843-y
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author Anita Madison
Carolyn Applegate
Victoria Stinnett
Diego Marrero Miranda
Chantal Cross
Kamaria Cayton Vaught
Ying S. Zou
Jaclyn B. Murry
author_facet Anita Madison
Carolyn Applegate
Victoria Stinnett
Diego Marrero Miranda
Chantal Cross
Kamaria Cayton Vaught
Ying S. Zou
Jaclyn B. Murry
author_sort Anita Madison
collection DOAJ
description Abstract Individuals with Turner syndrome (TS) phenotypes may exhibit short stature, ovarian dysfunction, and neurocognitive disorders. Their genomes can include ring chromosomes formed from the X chromosome (RCX). Here, we present cytogenomic and clinical findings from seventeen individuals with TS who bore mosaic forms of RCX and frequently presented with short stature and concern for TS. The subjects were retrospectively included and tested at a single-site cytogenetics laboratory for over 42 years. Here, we illustrate each subject’s comprehensive cytogenetic workup and phenotypes. The cohort shows comorbidities and sexual characteristics associated with mosaic RCX. These cytogenetic findings and clinical features are distinct from those of individuals with non-mosaic TS. Studying the pattern of X-activation across tissues in this cohort could provide additional data on a postulated source of phenotypic variability. Current guidelines recommend karyotype as the first-line test rather than SNP microarray analysis when aneuploidy is suspected. Conventional cytogenetics is still necessary to understand structural abnormalities, provide genomic context, and detect low-level mosaicism. These cases add to the knowledge of mosaic RCXs and offer new clinical laboratory information that is important for diagnosis and useful for comprehensively caring for and managing TS patients.
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spelling doaj-art-acabdc78daf54f7186eb95fb63612cba2025-08-20T03:18:23ZengNature PortfolioScientific Reports2045-23222025-04-011511910.1038/s41598-025-89843-yCytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institutionAnita Madison0Carolyn Applegate1Victoria Stinnett2Diego Marrero Miranda3Chantal Cross4Kamaria Cayton Vaught5Ying S. Zou6Jaclyn B. Murry7Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns Hopkins HospitalDepartment of Genetic Medicine, Johns Hopkins HospitalDepartment of Pathology, Cytogenomics Laboratory, Johns Hopkins HospitalDepartment of Molecular and Cell Biology, Krieger School of Arts and Sciences, Johns Hopkins UniversityDivision of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns Hopkins HospitalDivision of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Johns Hopkins HospitalDepartment of Pathology, Cytogenomics Laboratory, Johns Hopkins HospitalDepartment of Pathology, Cytogenomics Laboratory, Johns Hopkins HospitalAbstract Individuals with Turner syndrome (TS) phenotypes may exhibit short stature, ovarian dysfunction, and neurocognitive disorders. Their genomes can include ring chromosomes formed from the X chromosome (RCX). Here, we present cytogenomic and clinical findings from seventeen individuals with TS who bore mosaic forms of RCX and frequently presented with short stature and concern for TS. The subjects were retrospectively included and tested at a single-site cytogenetics laboratory for over 42 years. Here, we illustrate each subject’s comprehensive cytogenetic workup and phenotypes. The cohort shows comorbidities and sexual characteristics associated with mosaic RCX. These cytogenetic findings and clinical features are distinct from those of individuals with non-mosaic TS. Studying the pattern of X-activation across tissues in this cohort could provide additional data on a postulated source of phenotypic variability. Current guidelines recommend karyotype as the first-line test rather than SNP microarray analysis when aneuploidy is suspected. Conventional cytogenetics is still necessary to understand structural abnormalities, provide genomic context, and detect low-level mosaicism. These cases add to the knowledge of mosaic RCXs and offer new clinical laboratory information that is important for diagnosis and useful for comprehensively caring for and managing TS patients.https://doi.org/10.1038/s41598-025-89843-yArrayCMARingX chromosomeTurner syndrome
spellingShingle Anita Madison
Carolyn Applegate
Victoria Stinnett
Diego Marrero Miranda
Chantal Cross
Kamaria Cayton Vaught
Ying S. Zou
Jaclyn B. Murry
Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution
Scientific Reports
Array
CMA
Ring
X chromosome
Turner syndrome
title Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution
title_full Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution
title_fullStr Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution
title_full_unstemmed Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution
title_short Cytogenomic characterization of mosaic X-ring chromosomes in seventeen patients with Turner syndrome (TS)-42 years of experience at a single-site institution
title_sort cytogenomic characterization of mosaic x ring chromosomes in seventeen patients with turner syndrome ts 42 years of experience at a single site institution
topic Array
CMA
Ring
X chromosome
Turner syndrome
url https://doi.org/10.1038/s41598-025-89843-y
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