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Hailey-Hailey disease (HHD) is a rare, late-onset autosomal dominant genodermatosis characterized by blisters, vesicular lesions, crusted erosions, and erythematous scaly plaques predominantly in intertriginous regions. HHD is caused by ATP2C1mutations. About 180 distinct mutations have been identified so far; however, data of only few cases from Central Europe are available. The aim was to analyze the ATP2C1gene in a cohort of Polish HHD patients. A group of 18 patients was enrolled in the study based on specific clinical symptoms. Mutations were detected using Sanger or next generation sequencing. In silico analysis was performed by prediction algorisms and dynamic structural modeling. In two cases, mRNA analysis was performed to confirm aberrant splicing. We detected 13 different mutations, including 8 novel, 2 recurrent (p.Gly850Ter and c.325-3 T > G), and 6 sporadic (c.423-1G > T, c.899 + 1G > A, p.Leu539Pro, p.Thr808TyrfsTer16, p.Gln855Arg and a complex allele: c.[1610C > G;1741 + 3A > G]). In silico analysis shows that all novel missense variants are pathogenic or likely pathogenic. We confirmed pathogenic status for two novel variants c.325-3 T > G and c.[1610C > G;1741 + 3A > G] by mRNA analysis. Our results broaden the knowledge about genetic heterogeneity in Central European patients with ATP2C1mutations and also give further evidence that careful and multifactorial evaluation of variant pathogenicity status is essential.

Cystic fibrosis (CF) is one of the most common autosomal recessive diseases among Caucasians caused by a mutation in theCFTRgene. However, the clinical outcome of CF pulmonary disease varies remarkably even in patients with the sameCFTRgenotype. This has led to a search for genetic modifiers located outside theCFTRgene. The aim of this study was to evaluate the effect of functional variants in prostaglandin-endoperoxide synthase genes (COX1andCOX2) on the severity of lung disease in CF patients. To the best of our knowledge, it is the first time when analysis ofCOX1andCOX2as potential CF modifiers is provided. The study included 94 CF patients homozygous for F508del mutation ofCFTR. To compare their clinical condition, several parameters were recorded, e.g. a unique clinical score: disease severity status (DSS). To analyse the effect of non-CFTRgenetic polymorphisms on the clinical course of CF patients, the whole coding region ofCOX1and selectedCOX2polymorphisms were analysed. Statistical analysis of genotype-phenotype associations revealed a relationship between the heterozygosity status of identified polymorphisms and better lung function. These results mainly concernCOX2polymorphisms: −765G>C and 8473T>C. TheCOX1andCOX2polymorphisms reducing COX protein levels had a positive effect on all analysed clinical parameters. This suggests an important role of these genes as protective modifiers of pulmonary disease in CF patients, due to inhibition of arachidonic acid conversion into prostaglandins, which probably reduces the inflammatory process.