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: Jakob Usemann, Thomas Ernst, Vivien Schäfer, Kai Lehmberg, Karl Seeger
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 170A Issue 5 Pg. 1274-7 (May 2016) ISSN: 1552-4833 [Electronic] United States
• PMID: 26762561 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein

Topics

• Abnormalities, Multiple (genetics, physiopathology)
• Adolescent
• Amino Acid Substitution (genetics)
• Congenital Hypothyroidism (complications, genetics, physiopathology)
• Craniofacial Abnormalities (complications, genetics, physiopathology)
• Enhancer of Zeste Homolog 2 Protein (genetics)
• Female
• Hand Deformities, Congenital (complications, genetics, physiopathology)
• Humans
• Leukemia, Myeloid, Acute (complications, genetics, physiopathology)
• Lymphohistiocytosis, Hemophagocytic (complications, genetics, physiopathology)