Severe combined immunodeficiency associated with nephrogenic diabetes insipidus and a deletion in the Xq28 region

Clin Immunol. 2006 Aug;120(2):147-55. doi: 10.1016/j.clim.2006.05.001. Epub 2006 Jun 15.


We evaluated a baby boy with severe combined immunodeficiency (SCID) and X-linked nephrogenic diabetes insipidus (NDI). This patient had less than 10% CD3+ T cells, almost all of which were positive for CD4 and CD45RO. Genetic studies demonstrated a 34.4 kb deletion at Xq28 which included AVPR2, the gene responsible for NDI; ARHGAP4, a hematopoietic specific gene encoding a GTPase-activating protein; and a highly conserved segment of DNA between ARHGAP4 and ARD1A, a gene involved in the response to hypoxia. Other patients with NDI, but without immunodeficiency, have had deletions that remove all ARHGAP4 except exon 1; however, no other patients have had deletions of the highly conserved intragenic region between ARHGAP4 and ARD1A. X chromosome inactivation studies, done on sorted cells from the mother and grandmother of the patient, carriers of the deletion, demonstrated exclusive use of the non-mutant X chromosome as the active X in CD4 and CD8 T cells. Surprisingly, NK cells, monocytes and neutrophils from these women demonstrated preferential use of the mutant X chromosome as the active X. These results are consistent with an X-linked form of SCID, due to the loss of regulatory elements that control the response to hypoxia in hematopoietic cells.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Base Sequence
  • Child, Preschool
  • Chromosomes, Human, X / genetics*
  • Conserved Sequence
  • Diabetes Insipidus, Nephrogenic / complications
  • Diabetes Insipidus, Nephrogenic / genetics*
  • Down-Regulation
  • Exons / genetics
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Gene Deletion
  • Genes, X-Linked
  • Humans
  • Male
  • Molecular Sequence Data
  • N-Terminal Acetyltransferase A
  • N-Terminal Acetyltransferase E
  • Neural Cell Adhesion Molecule L1 / genetics
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Receptors, Vasopressin / genetics
  • Receptors, Vasopressin / metabolism
  • Severe Combined Immunodeficiency / complications
  • Severe Combined Immunodeficiency / genetics*


  • ARHGAP4 protein, human
  • GTPase-Activating Proteins
  • Neural Cell Adhesion Molecule L1
  • Receptors, Vasopressin
  • Acetyltransferases
  • N-Terminal Acetyltransferase A
  • NAA10 protein, human
  • N-Terminal Acetyltransferase E