Prenatal diagnosis in two families with autosomal, p47phox-deficient chronic granulomatous disease due to a novel point mutation in NCF1

Martin De Boer, Vinita Singh, Jan Dekker, Maja Di Rocco, David Goldblatt, Dirk Roos

Research output: Contribution to journalArticle

Abstract

Objective: Prenatal diagnosis was required in two unrelated families with chronic granulomatous disease (CGD) patients who lacked expression of p47phox 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 p47Phox-deficient CGD was confirmed on DNA extracted from fetal blood. Conclusion: This is the first report of prenatal diagnosis in p47 phox-deficient CGD.

Original languageEnglish
Pages (from-to)235-240
Number of pages6
JournalPrenatal Diagnosis
Volume22
Issue number3
DOIs
Publication statusPublished - 2002

Keywords

  • Chronic granulomatous disease
  • NCF1 locus
  • p47

ASJC Scopus subject areas

  • Genetics(clinical)
  • Obstetrics and Gynaecology

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