PMID- 10089913
OWN - NLM
STAT- MEDLINE
DCOM- 19990421
LR  - 20191024
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 27
IP  - 3
DP  - 1999 Mar
TI  - Uncommon missense and splice mutations and resulting biochemical phenotypes in
      German patients with X-linked chronic granulomatous disease.
PG  - 505-11
AB  - Chronic granulomatous disease is an inherited disease characterized by the
      inability of phagocytes to generate normal amounts of superoxide, leaving
      patients susceptible to opportunistic, life-threatening infections. In the
      majority of cases, cytochrome b558 is absent in the X-chromosomal form of CGD.
      However, the neutrophils from six of nine X-linked CGD patients, reported here,
      expressed normal or decreased amounts of this cytochrome and are referred to as
      "variant" forms. In three of these six variant patients, a roughly proportional
      decrease in cytochrome b558 expression and production of H2O2 were found. In two 
      cases this phenotype could be well explained by special splice mutations, whereas
      in the third case it was caused by a missense mutation, predicting Ser 193-->Phe.
      In the other three variant patients, cytochrome b558 expression and H2O2
      production were clearly disproportionate as the generation of H2O2 was much more 
      decreased than cytochrome expression. Missense mutations also were found in these
      cases. One of these mutations, predicting Leu 546-->Pro and affecting the
      putative nicotinamide adenine dinucleotide phosphate binding site, led to normal 
      levels of cytochrome b558 expression and reduced H2O2 production. In the other
      two mutations, predicting Pro 339-->His and His 338-->Tyr, the putative flavin
      adenine dinucleotide binding site was affected. This could explain the
      corresponding uncommon phenotypes, characterized by zero or trace amounts of H2O2
      production and the expression of relatively high amounts of nonfunctional or low 
      functional cytochrome b558, respectively. The only missense mutation found that
      prevented the expression of any cytochrome b558 was caused by a predicted His
      222-->Arg exchange in one of the three classic cases. The two other classic
      phenotypes were caused by splice mutations.
FAU - Roesler, J
AU  - Roesler J
AD  - Department of Pediatrics, Clinic of the University of Dresden, Germany.
FAU - Heyden, S
AU  - Heyden S
FAU - Burdelski, M
AU  - Burdelski M
FAU - Schafer, H
AU  - Schafer H
FAU - Kreth, H W
AU  - Kreth HW
FAU - Lehmann, R
AU  - Lehmann R
FAU - Paul, D
AU  - Paul D
FAU - Marzahn, J
AU  - Marzahn J
FAU - Gahr, M
AU  - Gahr M
FAU - Rosen-Wolff, A
AU  - Rosen-Wolff A
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (Cytochrome b Group)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 11062-77-4 (Superoxides)
RN  - 53-59-8 (NADP)
RN  - 9064-78-2 (cytochrome b558)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.6.3.- (CYBB protein, human)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amino Acid Substitution
MH  - Binding Sites
MH  - Child
MH  - Child, Preschool
MH  - Cytochrome b Group/deficiency/*genetics
MH  - Dosage Compensation, Genetic
MH  - Female
MH  - Gene Frequency
MH  - *Genetic Heterogeneity
MH  - Genotype
MH  - Germany
MH  - Granulomatous Disease, Chronic/*genetics
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Macromolecular Substances
MH  - Male
MH  - Membrane Glycoproteins/deficiency/*genetics
MH  - Middle Aged
MH  - NADP/metabolism
MH  - NADPH Oxidase 2
MH  - NADPH Oxidases/deficiency/*genetics
MH  - Phenotype
MH  - *Point Mutation
MH  - RNA Splicing
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Reactive Oxygen Species
MH  - Superoxides/metabolism
MH  - X Chromosome/*genetics
EDAT- 1999/03/25 00:00
MHDA- 1999/03/25 00:01
CRDT- 1999/03/25 00:00
PHST- 1999/03/25 00:00 [pubmed]
PHST- 1999/03/25 00:01 [medline]
PHST- 1999/03/25 00:00 [entrez]
AID - S0301-472X(98)00024-1 [pii]
AID - 10.1016/s0301-472x(98)00024-1 [doi]
PST - ppublish
SO  - Exp Hematol. 1999 Mar;27(3):505-11. doi: 10.1016/s0301-472x(98)00024-1.