PMID- 10598813
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 105
IP  - 5
DP  - 1999 Nov
TI  - Autosomal recessive chronic granulomatous disease caused by novel mutations in
      NCF-2, the gene encoding the p67-phox component of phagocyte NADPH oxidase.
PG  - 460-7
AB  - Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency disease 
      that leads to severe recurrent infections. CGD is caused by defects in the
      phagocyte NADPH oxidase, a multiprotein enzyme that reduces oxygen to superoxide,
      a precursor of microbicidal oxidants. Less than 6% of CGD patients have an
      autosomal recessive form of the disease caused by mutations in NCF-2. This gene
      encodes p67-phox, a cytosolic oxidase subunit that associates with membrane-bound
      flavocytochrome b558 and regulates electron transfer. We studied six patients
      from five families with p67-phox deficiency and identified seven different mutant
      alleles. Patients from three of the kindreds were homozygous for their respective
      mutation, although the parents of only one family were known to be related. Five 
      of the mutations have not previously been identified: (1) a missense mutation
      (383C-->T) in exon 5, (2) a nonsense mutation (196C-->T) in exon 3, (3) a
      missense mutation (230G-->A) in exon 3, (4) a nonsense mutation (298C-->T) in
      exon 4, and (5) a dinucleotide deletion (835-836 AC) from exon 9. Phagocytes from
      each of the patients analyzed failed to generate a measurable respiratory burst
      and had no detectable p67-phox protein. Our results further demonstrate that
      there is great heterogeneity among the mutations in p67-phox-deficient CGD
      patients, with no evidence for mutational hot-spots or a founder effect. Our data
      also support the hypothesis that the stability of p67-phox is particularly
      sensitive to missense mutations that cause amino acid substitutions within its
      N-terminal domain. In contrast, mutations predicting single amino acid changes
      elsewhere in the protein generally represent benign polymorphisms.
FAU - Noack, D
AU  - Noack D
AD  - Department of Molecular and Experimental Medicine, The Scripps Research
      Institute, La Jolla, CA 92037, USA.
FAU - Rae, J
AU  - Rae J
FAU - Cross, A R
AU  - Cross AR
FAU - Munoz, J
AU  - Munoz J
FAU - Salmen, S
AU  - Salmen S
FAU - Mendoza, J A
AU  - Mendoza JA
FAU - Rossi, N
AU  - Rossi N
FAU - Curnutte, J T
AU  - Curnutte JT
FAU - Heyworth, P G
AU  - Heyworth PG
LA  - eng
SI  - GENBANK/M32011
GR  - AI24838/AI/NIAID NIH HHS/United States
GR  - CA68276/CA/NCI NIH HHS/United States
GR  - RR00833/RR/NCRR NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (Codon, Nonsense)
RN  - 0 (Phosphoproteins)
RN  - 0 (neutrophil cytosol factor 67K)
RN  - 9007-49-2 (DNA)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Child
MH  - Child, Preschool
MH  - Codon, Nonsense
MH  - DNA/genetics
MH  - Enzyme Stability/genetics
MH  - Female
MH  - Genes, Recessive
MH  - Granulomatous Disease, Chronic/*enzymology/*genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Mutation, Missense
MH  - NADPH Oxidases/deficiency/*genetics
MH  - Phagocytes/enzymology
MH  - Phosphoproteins/deficiency/*genetics
MH  - Sequence Deletion
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1007/s004390051131 [doi]
PST - ppublish
SO  - Hum Genet. 1999 Nov;105(5):460-7. doi: 10.1007/s004390051131.