Somatic triple mosaicism in a carrier of X-linked chronic granulomatous disease

Blood. 1998 Jan 1;91(1):252-7.

Abstract

The X-linked form of chronic granulomatous disease (CGD) is caused by mutations in the CYBB gene, which encodes the 91-kD subunit of the flavocytochrome b558, a component of the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytic leukocytes. Mutations in this gene are very heterogeneous and often unique for one family. Here we report on a family with two patients (brothers), one with a 3-kb deletion comprising exon 5 and the other with a 3.5-kb deletion comprising exons 6 and 7 of the CYBB gene. Sequence analysis of polymerase chain reaction (PCR)-amplified genomic DNA proved these deletions to be overlapping for 35 bp. Analysis by restriction fragment length polymorphism of genomic DNA from the mother's leukocytes showed her to be a carrier of both deletions in addition to the normal CYBB sequence. This triple somatic mosaicism was confirmed with PCR-amplified genomic and complementary DNA. The presence of the normal CYBB gene in the mother was also proven by the finding of normal superoxide-generating neutrophils in addition to cells lacking this ability. Triple X syndrome was excluded. These findings suggest that the mutations are the result of an event in early embryogenesis of the mother, possibly involving a mechanism like sister chromatid exchange.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Cytochrome b Group / deficiency
  • Cytochrome b Group / genetics*
  • DNA Mutational Analysis
  • Exons / genetics
  • Fatal Outcome
  • Female
  • Granulomatous Disease, Chronic / genetics*
  • Heterozygote
  • Humans
  • Male
  • Mosaicism / genetics*
  • NADPH Oxidases*
  • Neutrophils / metabolism
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Sister Chromatid Exchange
  • Superoxides / metabolism
  • X Chromosome / genetics*

Substances

  • Cytochrome b Group
  • Superoxides
  • cytochrome b558
  • NADPH Oxidases