title: EZH2 mutation in an adolescent with Weaver syndrome developing acute myeloid leukemia and secondary hemophagocytic lymphohistiocytosis.
abstract: 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.
authors.affiliation: Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|University Children's Hospital (UKBB) Basel, Basel, Switzerland.
authors.forename: Jakob
authors.initials: J
authors.lastname: Usemann
authors.affiliation: Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.affiliation: Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Vivien
authors.initials: V
authors.lastname: Schäfer
authors.affiliation: Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Lehmberg
authors.affiliation: Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Seeger
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D003409:Congenital Hypothyroidism / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D019465:Craniofacial Abnormalities / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics*; D005260:Female; D006228:Hand Deformities, Congenital / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
chemical_list: C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: EZH2; Weaver syndrome; acute myeloid leukemia; hemophagocytic lymphohistiocytosis; malignancy; overgrowth