Blood Journal
Leading the way in experimental and clinical research in hematology

The phenotype of human STK4 deficiency

  1. Hengameh Abdollahpour1,
  2. Giridharan Appaswamy1,
  3. Daniel Kotlarz1,2,
  4. Jana Diestelhorst1,2,
  5. Rita Beier1,
  6. Alejandro A. Schäffer3,
  7. E. Michael Gertz3,
  8. Axel Schambach4,
  9. Hans H. Kreipe5,
  10. Dietmar Pfeifer6,
  11. Karin R. Engelhardt7,
  12. Nima Rezaei8,
  13. Bodo Grimbacher7,
  14. Sabine Lohrmann9,
  15. Roya Sherkat10, and
  16. Christoph Klein1,2
  1. 1Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany;
  2. 2University Children's Hospital Munich, Dr von Haunersches Kinderspital, Munich, Germany;
  3. 3National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, MD;
  4. 4Department of Experimental Hematology, Hannover Medical School, Hannover, Germany;
  5. 5Institute of Pathology, Hannover Medical School, Hannover, Germany;
  6. 6Department of Hematology/Oncology, Core Facility II Genomics, Freiburg University Medical Center, Freiburg, Germany;
  7. 7Department of Immunology and Molecular Pathology, Royal Free Hospital & University College London, London, United Kingdom;
  8. 8Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran;
  9. 9Department of Pediatric Cardiology, Hannover Medical School, Hannover, Germany; and
  10. 10Infectious Diseases Research Center, Department of Infectious Diseases, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in 3 members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts, and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome.

  • Submitted September 7, 2011.
  • Accepted January 16, 2012.
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