Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency

• Published in: Blood Vol. 118; no. 10; pp. 2656 - 2658
• Main Authors: Dickinson, Rachel Emma, Griffin, Helen, Bigley, Venetia, Reynard, Louise N., Hussain, Rafiqul, Haniffa, Muzlifah, Lakey, Jeremy H., Rahman, Thahira, Wang, Xiao-Nong, McGovern, Naomi, Pagan, Sarah, Cookson, Sharon, McDonald, David, Chua, Ignatius, Wallis, Jonathan, Cant, Andrew, Wright, Michael, Keavney, Bernard, Chinnery, Patrick F., Loughlin, John, Hambleton, Sophie, Santibanez-Koref, Mauro, Collin, Matthew
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 08.09.2011; Americain Society of Hematology
• Subjects: B-Lymphocytes - pathology; Biological and medical sciences; Dendritic Cells - pathology; Disease Susceptibility - etiology; Exons - genetics; GATA2 Transcription Factor - chemistry; GATA2 Transcription Factor - genetics; Hematologic and hematopoietic diseases; Humans; Killer Cells, Natural - pathology; Lymphoid Tissue - pathology; Medical sciences; Monocytes - pathology; Mutation - genetics; Protein Conformation; Natural killer cell; Dendritic cell; Transcription factor GATA2; Hematology; Monocyte; Antigen presenting cell; Deficiency; Genetics; B-Lymphocyte; Mutation; Sequencing
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-06-360313

The human syndrome of dendritic cell, monocyte, B and natural killer lymphoid deficiency presents as a sporadic or autosomal dominant trait causing susceptibility to mycobacterial and other infections, predisposition to myelodysplasia and leukemia, and, in some cases, pulmonary alveolar proteinosis. Seeking a genetic cause, we sequenced the exomes of 4 unrelated persons, 3 with sporadic disease, looking for novel, heterozygous, and probably deleterious variants. A number of genes harbored novel variants in person, but only one gene, GATA2, was mutated in all 4 persons. Each person harbored a different mutation, but all were predicted to be highly deleterious and to cause loss or mutation of the C-terminal zinc finger domain. Because GATA2 is the only common mutated gene in 4 unrelated persons, it is highly probable to be the cause of dendritic cell, monocyte, B, and natural killer lymphoid deficiency. This disorder therefore constitutes a new genetic form of heritable immunodeficiency and leukemic transformation.