EZH2 Mutation in an Adolescent with Weaver Syndrome Developing Acute Myeloid Leukemia and Secondary Hemophagocytic Lymphohistiocytosis
EZH2 Mutation in an Adolescent with Weaver Syndrome Developing Acute Myeloid Leukemia and Secondary Hemophagocytic Lymphohistiocytosis
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DOI：
10.1002/ajmg.a.37562
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发表时间：
2016-05-01
影响因子：
2
通讯作者：
Seeger, Karl
中科院分区：
文献类型：
--
作者：
Usemann, Jakob;Ernst, Thomas;Seeger, Karl
Weaver综合征是一种以出生前和出生后过度生长为特征的生长过度综合征，具有独特的头面部外观。ZEST同源基因增强子2(EZH2)基因的突变被发现是引起Weaver综合征的原因，并与包括急性髓系白血病(AML)在内的血液系统恶性肿瘤有关。我们提出了第一例Weaver综合征患者的报告，他发展为AML并携带EZH2突变。这位16岁的青春期女性患者的临床过程并发继发性噬血细胞性淋巴组织细胞增多症。AML确诊时，从骨髓细胞中提取基因组DNA。用覆盖EZH2基因所有外显子的引物进行聚合酶链式反应。我们在第5外显子中发现了一个新的杂合子EZH2突变，该突变导致催化D1区132位(p.Pro132Leu)的氨基酸从Pro变为亮氨酸。对缓解期样本的分析也显示了这种突变，表明是生殖系突变。在特定的AML病例中，EZH2突变是否与疾病严重程度有关仍有待阐明。(C)2016威利期刊公司。
Weaver syndrome is an overgrowth syndrome characterized by pre- and postnatal overgrowth with distinctive craniofacial appearance. Mutations in the enhancer of zeste homolog 2 (EZH2) gene were found to cause Weaver syndrome, and have been associated with hematologic malignancies, including acute myeloid leukemia (AML). We present the first report of a patient with Weaver syndrome, who developed AML and harbored an EZH2 mutation. The clinical course of the 16-year-old female adolescent patient was complicated by a secondary hemophagocytic lymphohistiocytosis. Genomic DNA was isolated from bone marrow cells at AML diagnosis. Polymerase chain reactions were performed with primers covering all exons of the EZH2 gene. We found a novel heterozygous EZH2 mutation within exon 5 that caused an amino acid change from proline to leucine at position 132 (p.Pro132Leu) within the catalytic D1 domain. Analysis of a remission sample also showed this mutation, indicating a germline mutation. It remains to be elucidated whether EZH2 mutations contribute to disease severity in specific AML cases. (C) 2016 Wiley Periodicals, Inc.