Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency
Year: 2011
Type: article
Abstract: 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.
Source: Blood
Authors: Rachel Emma Dickinson, Helen Griffin, Venetia Bigley, Louise N. Reynard, Rafiqul Hussain, Muzlifah Haniffa, Jeremy H. Lakey, Thahira Rahman, Xiao-Nong Wang, Naomi McGovern, Sarah Pagan, Sharon Cookson, David McDonald, Ignatius Chua, Jonathan Wallis, Andrew Cant, Michael Wright, Bernard Keavney, Patrick F. Chinnery, John Loughlin, Sophie Hambleton, Mauro Santibanez-Koref, Matthew Collin
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2045264636