False-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-up

Abstract Background Interphase fluorescence in situ hybridization (FISH) is commonly used for rapid aneuploidy detection in clinical settings. While FISH-based aneuploidy detection provides rapid results desirable for patient management, it usually only utilizes one probe per chromosome, which may l...

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Main Authors: Qiliang Ding, Abigail L. Bronson, Kyna A. Byerly, Anna A. Essendrup, Elyse B. Mitchell, Cassandra K. Runke, Ross A. Rowsey, Nicole L. Hoppman
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Molecular Cytogenetics
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Online Access:https://doi.org/10.1186/s13039-024-00697-x
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author Qiliang Ding
Abigail L. Bronson
Kyna A. Byerly
Anna A. Essendrup
Elyse B. Mitchell
Cassandra K. Runke
Ross A. Rowsey
Nicole L. Hoppman
author_facet Qiliang Ding
Abigail L. Bronson
Kyna A. Byerly
Anna A. Essendrup
Elyse B. Mitchell
Cassandra K. Runke
Ross A. Rowsey
Nicole L. Hoppman
author_sort Qiliang Ding
collection DOAJ
description Abstract Background Interphase fluorescence in situ hybridization (FISH) is commonly used for rapid aneuploidy detection in clinical settings. While FISH-based aneuploidy detection provides rapid results desirable for patient management, it usually only utilizes one probe per chromosome, which may lead to rare false-positive findings. Case presentation Here we report two interphase FISH results, which were false-positive for XXY in cytogenetically normal XX individuals. Both false-positive cases were due to hybridization of the Y chromosome centromeric probe DYZ3 to the pericentromeric region of chromosome 15. In both cases, chromosomal microarray revealed no detectable Y chromosome material, suggesting the hybridizations of the DYZ3 probe to chromosome 15 likely represent benign heterochromatic variants of no clinical significance. In one case, the DYZ3 hybridization was also identified in the phenotypically unaffected mother, further suggesting this is likely a rare variant of no clinical significance. Conclusions This report marks the first documentation of hybridization of the DYZ3 probe to another chromosome in cytogenetically normal individuals. Our report has important clinical implications, because DYZ3 is widely used by clinical laboratories for Y chromosome detection. Our findings underscore the necessity of confirming abnormal aneuploidy detection FISH results with additional laboratory methods such as chromosomal microarray analysis.
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spelling doaj-art-de3c40ccc0fd493fa7bf0c2e0556d1a82024-11-17T12:50:06ZengBMCMolecular Cytogenetics1755-81662024-11-011711610.1186/s13039-024-00697-xFalse-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-upQiliang Ding0Abigail L. Bronson1Kyna A. Byerly2Anna A. Essendrup3Elyse B. Mitchell4Cassandra K. Runke5Ross A. Rowsey6Nicole L. Hoppman7Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo ClinicAbstract Background Interphase fluorescence in situ hybridization (FISH) is commonly used for rapid aneuploidy detection in clinical settings. While FISH-based aneuploidy detection provides rapid results desirable for patient management, it usually only utilizes one probe per chromosome, which may lead to rare false-positive findings. Case presentation Here we report two interphase FISH results, which were false-positive for XXY in cytogenetically normal XX individuals. Both false-positive cases were due to hybridization of the Y chromosome centromeric probe DYZ3 to the pericentromeric region of chromosome 15. In both cases, chromosomal microarray revealed no detectable Y chromosome material, suggesting the hybridizations of the DYZ3 probe to chromosome 15 likely represent benign heterochromatic variants of no clinical significance. In one case, the DYZ3 hybridization was also identified in the phenotypically unaffected mother, further suggesting this is likely a rare variant of no clinical significance. Conclusions This report marks the first documentation of hybridization of the DYZ3 probe to another chromosome in cytogenetically normal individuals. Our report has important clinical implications, because DYZ3 is widely used by clinical laboratories for Y chromosome detection. Our findings underscore the necessity of confirming abnormal aneuploidy detection FISH results with additional laboratory methods such as chromosomal microarray analysis.https://doi.org/10.1186/s13039-024-00697-xAneuploidyInterphase FISHDYZ3XXYPrenatal diagnosis
spellingShingle Qiliang Ding
Abigail L. Bronson
Kyna A. Byerly
Anna A. Essendrup
Elyse B. Mitchell
Cassandra K. Runke
Ross A. Rowsey
Nicole L. Hoppman
False-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-up
Molecular Cytogenetics
Aneuploidy
Interphase FISH
DYZ3
XXY
Prenatal diagnosis
title False-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-up
title_full False-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-up
title_fullStr False-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-up
title_full_unstemmed False-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-up
title_short False-positive XXY results by interphase FISH in cytogenetically normal XX individuals: two cases highlighting the necessity of additional laboratory follow-up
title_sort false positive xxy results by interphase fish in cytogenetically normal xx individuals two cases highlighting the necessity of additional laboratory follow up
topic Aneuploidy
Interphase FISH
DYZ3
XXY
Prenatal diagnosis
url https://doi.org/10.1186/s13039-024-00697-x
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