Media type: E-Article Title: EZH2 mutation in an adolescent with Weaver syndrome developing acute myeloid leukemia and secondary hemophagocytic lymphohistiocytosis Contributor: Usemann, Jakob; Ernst, Thomas; Schäfer, Vivien; Lehmberg, Kai; Seeger, Karl Published: Wiley, 2016 Published in: American Journal of Medical Genetics Part A, 170 (2016) 5, Seite 1274-1277 Language: English DOI: 10.1002/ajmg.a.37562 ISSN: 1552-4825; 1552-4833 Origination: Footnote: Description: 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. © 2016 Wiley Periodicals, Inc.