Somatic Triple Mosaicism in a Carrier of X-Linked Chronic
Granulomatous Disease
Martin de Boer,
Egbert Bakker,
Stefaan Van Lierde, and
Dirk Roos
From the Central Laboratory of the Netherlands Red Cross Blood
Transfusion Service, and Laboratory for Experimental and Clinical
Immunology, Academic Medical Centre, University of Amsterdam,
Amsterdam, The Netherlands; the Department of Human Genetics,
University of Leiden, Leiden, The Netherlands; and the Department of
Pediatrics, University Hospital Leuven, Leuven, Belgium.
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.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 252-257
© 1998 by The American Society of Hematology.
