title: Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency.
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.
authors.affiliation: Institute of Cellular Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Rachel Emma
authors.initials: RE
authors.lastname: Dickinson
authors.forename: Helen
authors.initials: H
authors.lastname: Griffin
authors.forename: Venetia
authors.initials: V
authors.lastname: Bigley
authors.forename: Louise N
authors.initials: LN
authors.lastname: Reynard
authors.forename: Rafiqul
authors.initials: R
authors.lastname: Hussain
authors.forename: Muzlifah
authors.initials: M
authors.lastname: Haniffa
authors.forename: Jeremy H
authors.initials: JH
authors.lastname: Lakey
authors.forename: Thahira
authors.initials: T
authors.lastname: Rahman
authors.forename: Xiao-Nong
authors.initials: XN
authors.lastname: Wang
authors.forename: Naomi
authors.initials: N
authors.lastname: McGovern
authors.forename: Sarah
authors.initials: S
authors.lastname: Pagan
authors.forename: Sharon
authors.initials: S
authors.lastname: Cookson
authors.forename: David
authors.initials: D
authors.lastname: McDonald
authors.forename: Ignatius
authors.initials: I
authors.lastname: Chua
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wallis
authors.forename: Andrew
authors.initials: A
authors.lastname: Cant
authors.forename: Michael
authors.initials: M
authors.lastname: Wright
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
authors.forename: Sophie
authors.initials: S
authors.lastname: Hambleton
authors.forename: Mauro
authors.initials: M
authors.lastname: Santibanez-Koref
authors.forename: Matthew
authors.initials: M
authors.lastname: Collin
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology*; D003713:Dendritic Cells / Q000473:pathology*; D004198:Disease Susceptibility / Q000209:etiology*; D005091:Exons / Q000235:genetics*; D050989:GATA2 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology*; D008221:Lymphoid Tissue / Q000473:pathology*; D009000:Monocytes / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D011487:Protein Conformation
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human