Cys244Ser and p.His338Tyr were detected. Furthermore, a deletion of exons 1–3 was observed as well as three different nonsense mutations p.Arg91X, p.Arg226X and p.Trp483X. Only two mothers were tested for carrier status. Interestingly, the mother of patient 13 (p.Trp483X) does not carry the mutation (data not shown) suggesting that the mutation has arisen spontaneously

in her germ line cells or in her son early during foetal development. Spontaneous mutations have previously been described [25]. Patient 17 carries a novel duplication of the 3′ part of CYBB, starting DZNeP in intron 8 and extending into exon 13, and leading to outsplicing of exon 13. Due to extremely lyonized expression of the defective gene, this female patient has only 9% cells with NADPH oxidase activity in the DHR test, but is without symptoms now. Finally, we have detected a mutation at the 3′ end of intron 3, affecting the splicing of exon 4. This mutation results in alternative splicing with omission of the first 14 bases of exon 4 in the mRNA and introduction of a stop codon in exon 4 [25]. OTX015 Ten patients were shown to have mutations in NCF1, and seven of these were homozygous for the common deletion of GT start exon 2

(Table 1). Patient 26 is compound heterozygous and carries the common deletion of GT at the start of exon 2 on one allele and a novel G>A mutation in the 5′ splice site in intron 7 on the other allele, leading to outsplicing of exon 7 from the mRNA (Fig. 2). At present, the patient has Roflumilast no symptoms, similar to the other patients homozygous for the GT deletion. Patient 18 is homozygous for a nonsense mutation p.Trp204X in exon 7 (for further details see [20]). Recently, the same mutation was detected in patient 19 at the DNA level. We were not able to confirm the mutation

on cDNA level due to lack of material. To our knowledge, the two patients are not related. The molecular background of the Danish patients with CGD followed in the clinic or newly diagnosed in a 5-year period was determined. A total of 27 patients with CGD were included, leading to a prevalence of CGD in Denmark of 1 in 215,000, which is a slightly higher prevalence than previously described in a recent European study with 1:250,000 [5] and much higher compared to Sweden with a reported prevalence in 1995 of 1:450,000[26]. Three patients died during the 5-year period of the study. Furthermore, we found that X-linked mutations accounted for 40% of the cases, whereas autosomal recessive mutations accounted for 60% of the cases. These data deviate from previously obtained results that show a distribution across the groups with 72% and 28% having X-linked and autosomal recessive CGD, respectively [9, 10]. The age range of the cohort is 14–60 years with only two patients being under 23 years. Therefore, it cannot be excluded that some patients with X-linked CGD may not have been included in the study because they died early due to the severity of their disease.