title: A founder effect for p47(phox)Trp193Ter chronic granulomatous disease in Kavkazi Jews.
abstract: Chronic granulomatous disease (CGD) is a rare congenital immune deficiency caused by mutations in any of the five genes encoding NADPH oxidase subunits. One of these genes is NCF1, encoding the p47(phox) protein. A group of 39 patients, 14 of whom are of Kavkazi Jewish descent, was investigated for a founder effect for the mutation c.579G>A (p.Trp193Ter) in NCF1. We analyzed various genetic markers in the NCF1 region, including two single nucleotide polymorphisms (SNPs) in NCF1 and two short tandem repeats (STRs) located near NCF1. Most patients were homozygous for the c.579G>A mutation, but three patients were hemizygotes, with a deletion of NCF1 on the other allele, and three patients were compound heterozygotes with another mutation in NCF1. All Kavkazi Jewish patients had a c.295G_c.345T SNP combination in NCF1 and shared a common number of repeats in STR3. In addition, 90% of the Kavkazi Jewish patients shared a common number of repeats in STR1. This uniformity indicates that the c.579G>A mutation in NCF1 was introduced some 1200-2300 years ago in the Kavkazi Jewish population. Variation amongst the other investigated populations from the Middle East indicates that this mutation exists in these non-Kavkazi populations already for more than 5000 years.
authors.affiliation: Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: de Boer
authors.affiliation: Dept. of Nephrology and Molecular Medicine, Rappaport Faculty of Medicine and Research Institute, Technion, and Rambam Medical Center, Haifa, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Tzur
authors.affiliation: Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: van Leeuwen
authors.affiliation: Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paula C D
authors.initials: PC
authors.lastname: Dencher
authors.affiliation: Dept. of Nephrology and Molecular Medicine, Rappaport Faculty of Medicine and Research Institute, Technion, and Rambam Medical Center, Haifa, Israel.
authors.forename: Karl
authors.initials: K
authors.lastname: Skorecki
authors.affiliation: Dept. of Pediatrics and Laboratory for Leukocyte Function, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Baruch
authors.initials: B
authors.lastname: Wolach
authors.affiliation: Dept. of Pediatrics and Laboratory for Leukocyte Function, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Gavrieli
authors.affiliation: Dept. of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Ivane
authors.initials: I
authors.lastname: Nasidze
authors.affiliation: Dept. of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Stoneking
authors.affiliation: Dept. of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Michael W T
authors.initials: MW
authors.lastname: Tanck
authors.affiliation: Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: d.roos@sanquin.nl.
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
mesh_terms: D000483:Alleles; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D023061:Gene Order; D056426:Genetic Loci; D005838:Genotype; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics*; D010375:Pedigree
chemical_list: D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: Chronic granulomatous disease; Founder effect; Kavkazi Jews; NADPH oxidase; NCF1; p47(phox)