Publication:

Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency (2011)

Author(s): Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M

    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.

      • Date: 15-07-2011
      • Journal: Blood
      • Volume: 118
      • Issue: 10
      • Pages: 2656-2658
      • Publisher: American Society of Hematology
      • Publication type: Article
      • Bibliographic status: Published
      Staff

      Professor Matthew Collin
      Professor of Haematology

      Professor Jeremy Lakey
      Professor of Structural Biochemistry