HSCT in two brothers with CGD arising from mutations in CYBC1 corrects the defect in neutrophil function

Clin Immunol. 2021 Aug:229:108799. doi: 10.1016/j.clim.2021.108799. Epub 2021 Jul 16.

Abstract

Homozygous mutations in cytochrome b-245 chaperone 1 (CYBC1) have been recently described as causing recurrent infections and inflammatory disease in an Icelandic cohort and a patient from Saudi Arabia, by destabilising the dimerisation of gp91phox with p22phox, manifesting as phenotypic chronic granulomatous disease (CGD). Haematopoietic stem cell transplantation is the treatment of choice in CGD, though experience of transplantation in this subtype of CGD is limited to a brief description in one patient. We provide clinical and transplant data for two Icelandic brothers with CGD due to homozygous p.Tyr2Ter mutations in CYBC1, demonstrating maintained cure of the immune defect 11 years post-transplant in one brother, and death in the peri-transplant period for the other.

Keywords: CGD; CYBC1; HSCT; Iceland; NADPH; Oxidative burst.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Fatal Outcome
  • Genetic Association Studies
  • Granulomatous Disease, Chronic / genetics*
  • Granulomatous Disease, Chronic / immunology
  • Granulomatous Disease, Chronic / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Homozygote
  • Humans
  • Iceland
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology*
  • Mutation*
  • Siblings

Substances

  • CYBC1 protein, human
  • Membrane Proteins