Kobayashi Kenichiro, Iwai Atsushi, Tanaka Kuniaki, Mizuta Shumpei, Yoshida Saya, Maihara Toshiro, Nishida Yoshinobu, Wada Takahito, Usami Ikuya, Heike Toshio
Department of Pediatrics, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
Department of Pediatric Hematology and Oncology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
Cytogenet Genome Res. 2022;162(11-12):625-631. doi: 10.1159/000531259. Epub 2023 May 27.
Transient abnormal myelopoiesis (TAM) is a unique neonatal leukemoid reaction caused by a pathognomonic GATA1 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 GATA1 mutation screening) can verify the specificity of cytogenetic testing for phenotypically normal neonates with TAM suspected of mosaicism.
短暂异常髓系造血（TAM）是一种独特的新生儿类白血病反应，由特征性的GATA1突变联合21三体的基因剂量效应引起，其21三体可为种系或体细胞来源。我们遇到一名表型正常的48,XYY,+21唐氏综合征新生儿，因隐匿性种系嵌合而发生TAM。种系成分内过度增殖的TAM存在高估偏差，使得嵌合比例的量化变得复杂。为了建立针对这种临床情况的工作流程，我们分析了与体细胞或低水平种系嵌合相关的TAM新生儿的细胞遗传学结果。我们表明，多步骤诊断程序（即对有或无植物血凝素培养的外周血标本进行配对细胞遗传学分析；对不止一种组织如颊黏膜进行系列细胞遗传学研究；以及基于互补DNA的GATA1突变筛查）可以验证对疑似嵌合的TAM表型正常新生儿进行细胞遗传学检测的特异性。
