Novel Mutation of ZAP-70-related Combined Immunodeficiency: First Case from the National Iranian Registry and Review of the Literature

Immunol Invest. 2017 Jan;46(1):70-79. doi: 10.1080/08820139.2016.1214962. Epub 2016 Oct 19.

Abstract

ZAP-70 deficiency is a rare autosomal recessive form of combined immunodeficiency (CID) characterized by selective absence of circulating CD8 T cells with low, normal, or increased CD4 T cells in peripheral blood. Up to now, 14 unique mutations in the ZAP70 gene have been identified in patients with ZAP-70-related CID. We present a 3-year-old boy with a history of recurrent bacterial infections and autoimmunity. Initial laboratory findings showed a normal total lymphocyte count, but low levels of CD8 and CD4 T cells and an abnormal lymphocyte proliferation response. Immunoglobulin levels were normal, but the specific antibody response was impaired. Whole exome sequencing revealed a mutation within the kinase domain of ZAP-70. ZAP-70 deficiency should be considered in infants and young children with recurrent bacterial infections, in spite of having palpable lymph nodes, a notable thymus shadow, and a normal total lymphocyte count.

Keywords: Immunodeficiency; ZAP-70; lymphocyte.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Autoimmune Diseases / genetics*
  • Bacterial Infections / genetics*
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Proliferation / genetics
  • Child, Preschool
  • DNA Mutational Analysis
  • Humans
  • Immunity, Humoral / genetics
  • Immunologic Deficiency Syndromes / genetics*
  • Iran
  • Male
  • Mutation / genetics*
  • Registries
  • ZAP-70 Protein-Tyrosine Kinase / genetics*

Substances

  • ZAP-70 Protein-Tyrosine Kinase