Discovery of single-gene inborn errors of immunity by next generation sequencing

Curr Opin Immunol. 2014 Oct:30:17-23. doi: 10.1016/j.coi.2014.05.004. Epub 2014 Jun 2.


Many patients with clinical and laboratory evidence of primary immunodeficiency do not have a gene specific diagnosis. The use of next generation sequencing, particularly whole exome sequencing, has given us an extraordinarily powerful tool to identify the disease-causing genes in some of these patients. At least 34 new gene defects have been identified in the last 4 years. These findings document the striking heterogeneity of the phenotype in patients with mutations in the same gene. In some cases this can be attributed to loss-of-function mutations in some patients, but gain-of-function mutations in others. In addition, the surprisingly high frequency of autosomal dominant immunodeficiencies with variable penetrance, and de novo mutations in disorders with a severe phenotype has been unmasked.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Exons
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / immunology
  • Genetic Heterogeneity
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Phenotype