Low-Level Germline 48,XYY,+21 Mosaicism Associated with Transient Abnormal Myelopoiesis in a Phenotypically Normal Neonate
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Published:2023-05-27
Issue:
Volume:
Page:1-7
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ISSN:1424-8581
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Container-title:Cytogenetic and Genome Research
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language:en
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Short-container-title:Cytogenet Genome Res
Author:
Kobayashi Kenichiro,Iwai Atsushi,Tanaka Kuniaki,Mizuta Shumpei,Yoshida Saya,Maihara Toshiro,Nishida Yoshinobu,Wada Takahito,Usami Ikuya,Heike Toshio
Abstract
Transient abnormal myelopoiesis (TAM) is a unique neonatal leukemoid reaction caused by a pathognomonic <i>GATA1</i> mutation in conjunction with the gene dosage effect of trisomy 21, which is either of germline or somatic origin. We encountered a 48,XYY,+21 phenotypically normal neonate with Down syndrome who developed TAM due to cryptic germline mosaicism. Quantification of the mosaic ratio was complicated by an overestimation bias of hyperproliferating TAM within the germline component. To establish a workflow for such a clinical scenario, we analyzed the cytogenetic findings of neonates with TAM associated with somatic or low-level germline mosaicism. We showed that multistep diagnostic procedures (i.e., paired cytogenetic analyses of peripheral blood specimens in culture with or without phytohemagglutinin; serial cytogenetic studies of more than one tissue, such as the buccal membrane; and complementary DNA-based <i>GATA1</i> mutation screening) can verify the specificity of cytogenetic testing for phenotypically normal neonates with TAM suspected of mosaicism.
Subject
Genetics (clinical),Genetics,Molecular Biology