TY - JOUR
T1 - Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency
AU - Dickinson, Rachel Emma
AU - Griffin, Helen
AU - Bigley, Venetia
AU - Reynard, Louise N.
AU - Hussain, Rafiqul
AU - Haniffa, Muzlifah
AU - Lakey, Jeremy H.
AU - Rahman, Thahira
AU - Wang, Xiao Nong
AU - McGovern, Naomi
AU - Pagan, Sarah
AU - Cookson, Sharon
AU - McDonald, David
AU - Chua, Ignatius
AU - Wallis, Jonathan
AU - Cant, Andrew
AU - Wright, Michael
AU - Keavney, Bernard
AU - Chinnery, Patrick F.
AU - Loughlin, John
AU - Hambleton, Sophie
AU - Santibanez-Koref, Mauro
AU - Collin, Matthew
N1 - , British Heart Foundation, United Kingdom, Medical Research Council, United Kingdom, Wellcome Trust, United Kingdom
PY - 2011/9/8
Y1 - 2011/9/8
N2 - 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.Anumber 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. © 2011 by The American Society of Hematology.
AB - 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.Anumber 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. © 2011 by The American Society of Hematology.
U2 - 10.1182/blood-2011-06-360313
DO - 10.1182/blood-2011-06-360313
M3 - Article
C2 - 21765025
SN - 0006-4971
VL - 118
SP - 2656
EP - 2658
JO - Blood
JF - Blood
IS - 10
ER -