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 ATP2C1 mutations. 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 ATP2C1 gene 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 ATP2C1 mutations and also give further evidence that careful and multifactorial evaluation of variant pathogenicity status is essential. Keywords Hailey-Hailey disease. ATP2C1. Genodermatosis The data that support the findings of this study are available from the corresponding author upon reasonable request.

Epidermolysis bullosa is a group of inherited blistering skin diseases resulting in most cases from missense mutations in KRT5 and KRT14 genes encoding the basal epidermal keratins 5 and 14. Here, we present a patient diagnosed with a localized subtype of epidermolysis bullosa simplex caused by a heterozygous mutation p.Ala428Asp in the KRT5 gene, that has not been previously identified. Moreover, a bioinformatic analysis of the novel mutation was performed, showing changes in the interaction network between the proteins. Identification of novel mutations and genotype‐phenotype correlations allow to better understanding of underlying pathophysiologic bases and is important for genetic counselling, patients’ management, and disease course prediction.

Usher syndrome is rare genetic disorder impairing two human senses, hearing and vision, with the characteristic late onset of vision loss. This syndrome is divided into three types. In all cases, the vision loss is postlingual, while loss of hearing is usually prelingual. The vestibular functions may also be disturbed in Usher type 1 and sometimes in type 3. Vestibular areflexia is helpful in making a proper diagnosis of the syndrome, but, often, the syndrome is misdiagnosed as a nonsyndromic hearing loss. Here, we present a Polish family with hearing loss, which was clinically classified as nonsyndromic. After excluding mutations in the DFNB1 locus, we implemented the next-generation sequencing method and revealed that hearing loss was syndromic and mutations in the USH2A gene indicate Usher syndrome. This research highlights the importance of molecular analysis in establishing a clinical diagnosis of congenital hearing loss.

Mental disorders participate in the development of psoriasis as predisposing factors; a correlation of dermatological diseases with pathological anxiety and stress was shown. The aim of this study is to find the associations between SNV in genes COMT (rs4680), DBH (rs141116007), CCKAR (rs1800857), CCKBR (rs1805002), and psoriasis. In our study The c 2 test revealed an association with psoriasis only for the COMT gene, which encodes catechol-O-methyltransferase. Results of polygenic analysis also showed a significant influence of gene polymorphism COMT (rs4680) in the development of psoriasis. The carrying of both alleles in combinations with alleles of other genes forms the strongly associated patterns. Besides, the G allele, both alone and in combination with other genes and / or A allele, forms markers of strong predisposition to the disease. The AA genotype in the meantime is protective. This indicates the dominant manifestation of the G allele in the case of psoriasis. The association of GA genotype of COMT gene with psoriasis found in our study has no direct explanation of its functional activities. The most interesting hypothesis, which could explain the effect of the GA heterozygote of the COMT gene on the pathogenesis of psoriasis, from our point of view, is the possibility of changing the activity of the heterodimer. Thus, it was shown that COMT enzyme can exist in three forms: a monomer, a membrane-bound monomer and a dimer. The structure of proteins COMT 158Val and COMT 158Met is different, which results in different affinity to substrates and different stability of the enzyme. Thus, patients with psoriasis have an increased excretion of adrenaline in stressful situations.