Prenatal diagnosis in two families with autosomal, p47(phox)-deficient chronic granulomatous disease due to a novel point mutation in NCF1.
OBJECTIVE
Prenatal diagnosis was required in two unrelated families with chronic granulomatous disease (CGD) patients who lacked expression of p47(phox) protein; thus a search for mutations in NCF1 was undertaken.


METHODS
Gene scanning was applied to establish the relative number of coding and pseudo-NCF1 genes. PCRs specific for coding NCF1 cDNA and coding NCF1 exon-7 genomic DNA were devised.


RESULTS
The normal 1:2 ratio of coding and pseudo-NCF1 genes was found in the patients. Sequencing of the RT-PCR product specific for mRNA from the coding NCF1 genes revealed a novel homozygous G579A mutation in both patients, changing the TGG codon for Trp193 into the TAG stop codon. This mutation was confirmed in genomic DNA. The parents of both patients were found to be heterozygotes for this mutation. In the chorionic villus DNA of the first family a heterozygous G579A mutation was found. Postpartum, functional NADPH oxidase tests were normal. In the second family, this mutation was present in homozygous form in the chorionic villus DNA. Following termination of the pregnancy, the diagnosis of p47(phox)-deficient CGD was confirmed on DNA extracted from fetal blood.


CONCLUSIONS
This is the first report of prenatal diagnosis in p47(phox)-deficient CGD.
de Boer
Martin
M
Central Laboratory of the Netherlands Blood Transfusion Service (CLB), and Laboratory for Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Singh
Vinita
V
Dekker
Jan
J
Di Rocco
Maja
M
Goldblatt
David
D
Roos
Dirk
D
D000293:Adolescent; D002648:Child; D015193:Chorionic Villi Sampling; D005091:Exons; D005260:Female; D005865:Gestational Age; D006105:Granulomatous Disease, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D006579:Heterozygote; D006801:Humans; D007621:Karyotyping; D008297:Male; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D010750:Phosphoproteins; D012333:RNA, Messenger; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1