(FV1:1), hepato- & splenomegalia Colectomized Also suffered from Neurofibromatosis Recklinghausen Gingival hypertrophia Acne Colectomi and ileostomia due to pancolitis; Bone marrow transplantation may 2010 Colectomized years ago Chronic pulmonary aspergillosis, died from respiratory insufficiency December 2011 Died February 2008 1994 diagnosed as Crohn’s disease, colectomized, BMN 673 recurrent severe pulmonary infections incl B. cepasia, Severe pulmonary insufficiency. Home oxygen treatment. CGD diagnosed post mortem Severe acne Proctocolitis with

fistulae. Colostomized Severe parodontitis. Total tooth extraction done deletion splice site del 75_76 GTc c.682+1G>A p.Tyr26HisfsX26 Del exon 7 p.Trp193_Gly228del [16] Novel Diagnosed in 2012 Recurrent mucocutaneus abscesses, chronic gingivitis but no pulmonary symptoms An overview of the clinical status for all patients is presented in Table 1. The clinical history of six of the patients has previously been described in detail[19-22]. Genomic DNA was isolated from whole blood collected in EDTA with the Wizard Genomic DNA isolation kit from Promega (Nacka, Sweden). Custom synthesized primers were ordered from Invitrogen (Taastrup, Denmark). The 5′-fluorescently labelled oligonucleotides

were ordered from Applied Biosystems (Stockholm, Sweden). The Gene Scan Selleck Erismodegib analysis was performed as previously described [20, 23]. The ratio of functional genes to pseudogenes was determined by calculating the peak areas corresponding to the two fragments differing by only 2 bp. The five genes encoding the components of the NADPH oxidase complex were analysed in a sequential pattern with amplification and sequencing methods previously described [20, 24]. The molecular background of the Danish patients diagnosed with CGD and followed in the clinic was investigated, this cohort includes 27 patients. Sixteen of 27 patients (59%) had autosomal recessive mutations located in Monoiodotyrosine either NCF1 or CYBA. No mutations were observed in NCF2 or NCF4. Eleven patients had an X-linked mutation of the CYBB gene (Table 1). The present ages of the patients range from 14 to 60 years. Three

different mutations were found in a group of six patients. Patients 3, 4, 5 and 6 are related and harbour the same missense mutation p.Ala124Val in exon 6 of CYBA. Patients 1 and 2 are unrelated and both have a mutation in the 5′ splice site in intron 4, leading to the deletion of exon 4 in the mRNA transcript (Fig. 1). The deletion of exon 4 does not change the reading frame. At present, both patients are without symptoms even though their DHR test is negative. Patient 2 is only heterozygous for the splice site mutation but harbours a deletion of exon 6 on the other allele. In accordance with this finding, carrier status for the splice site mutation was only detected in the mother (Fig. 1). Ten different mutations were detected in the 11 patients with X-linked CGD. Patients 8 and 9 are brothers and have the same missense mutation p.Pro56Leu.