Volume 11 - 2020 | https://doi.org/10.3389/fimmu.2020.00641 This article is part of the Research TopicAutoinflammatory Keratinization Disease (AiKD)View all 5 articles Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is a rare autosomal recessive skin disorder characterized by palmoplantar keratoderma and numerous papules distributed linearly in the arm folds and on the wrists the affected skin shows hypertrophy and hyperplasia of the spinous and horny epidermal layers with mild infiltration of inflammatory cells in the upper dermis There are 14 patients with KLICK syndrome described in the literature and they all carry the same nucleotide deletion is an ubiquitously expressed protein that functions as a chaperone for proteasome maturation KLICK syndrome is caused by a reduction in POMP levels that leads to proteasome insufficiency in differentiating keratinocytes It is noteworthy that POMP is also known to be the causative gene for proteasome-associated autoinflammatory syndrome-2 (PRAAS2) It is considered that the disrupted proteasome assembly caused by the POMP mutation might lead to both skin inflammation and then hyperkeratosis in KLICK syndrome Inflammation caused by the hyperactivation of innate immunity occasionally leads to inflammatory diseases of the skin recently denoted as autoinflammatory keratinization diseases (AiKDs) We propose that KLICK syndrome caused by the specific 1-bp nucleotide deletion mutation in the regulatory region of POMP might be in a spectrum of proteasome-associated phenotypes Autoinflammatory keratinization disease (AiKD) is an umbrella term recently introduced to describe inflammatory keratinization diseases caused by mutations in single genes associated with autoinflammatory diseases (6, 7). AiKDs are genetically heterogeneous, and their different subtypes show various clinical features, complications, and prognoses (8–11) We propose that KLICK syndrome associated with the POMP mutation be categorized as an AiKD Although the proposed mechanism of diseases is different (haploinsufficiency vs the clinical inflammatory phenotype of PRAID is similar to that of PRAAS PRAID has been considered as the proteasome-associated autoinflammatory syndrome-2 (PRAAS2 Comparison of two syndromes associated with POMP mutations several distinct phenotypes resulting from the different mutations in NLRP1 have been reported Although phenotype/genotype correlations are still unclear the pathogenesis of these skin inflammatory diseases is linked to gain of function in the NLRP1 inflammasome The suggestive pathogenesis of keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome as an autoinflammatory keratinization disease (AiKD) effective therapies will be established for patients with KLICK syndrome in the near future based on an understanding of the molecular pathogenesis of KLICK syndrome further clinical and laboratory investigations for the diagnosis and treatment of KLICK are needed TT and MA contributed conception and design of the study and read and approved the submitted version TT wrote the first draft of the manuscript This work was supported by Grant-in-Aid for Scientific Research (B) 18H02832 to MA and by Grant-in-Aid for Young Scientists 18K16058 to TT from the Japan Society for the Promotion of Science (JSPS) This work was also supported by funding from Advanced Research and Development Programs for Medical Innovation (AMED-CREST) 19gm0910002h0105 to MA This research was supported by AMED under Grant Numbers JP19ek0109281 and JP19ek0109295 The authors thank JSID's Fellowship Shiseido Research Grant 2019 The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2020.00641/full#supplementary-material autoinflammatory keratinization diseases; ER keratosis linearis with ichthyosis congenita and sclerosing keratoderma; PG proteasome-associated autoinflammatory syndrome; PRAID POMP-related autoinflammation and immune dysregulation disease; UPR Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK-syndrome): a rare autosomal recessive disorder of keratohyaline formation A single-nucleotide deletion in the POMP 5′ UTR causes a transcriptional switch and altered epidermal proteasome distribution in KLICK genodermatosis KLICK syndrome: recognizable phenotype and hot-spot POMP mutation Autoinflammatory keratinization diseases: An emerging concept encompassing various inflammatory keratinization disorders of the skin Familial or sporadic porokeratosis as an autoinflammatory keratinization disease A novel NCSTN missense mutation in the signal peptide domain causes hidradenitis suppurativa which has features characteristic of an autoinflammatory keratinization disease Aberrant CARD14 function might cause defective barrier formation Pityriasis rubra pilaris type V as an autoinflammatory disease by CARD14 mutations Congenital ichthyosiform dermatosis with linear keratotic flexural papules and sclerosing palmoplantar keratoderma CrossRef Full Text | Google Scholar [Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK syndrome)] Heterozygous truncating variants in POMP escape nonsense-mediated decay and cause a unique immune dysregulatory syndrome Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity Crosstalk and interplay between the ubiquitin-proteasome system and autophagy Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress siRNA silencing of proteasome maturation protein (POMP) activates the unfolded protein response and constitutes a model for KLICK genodermatosis recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome Unfolded protein response in keratinocytes: impact on normal and abnormal keratinization Insights into the role of endoplasmic reticulum stress in skin function and associated diseases Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production PSMB8 encoding the beta5i proteasome subunit is mutated in joint contractures and panniculitis-induced lipodystrophy syndrome Nakajo-Nishimura syndrome: an autoinflammatory disorder showing pernio-like rashes and progressive partial lipodystrophy Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder CANDLE Syndrome As a Paradigm of Proteasome-Related Autoinflammation the last immunoproteasome gene missing for PRAAS IFN-gamma-induced immune adaptation of the proteasome system is an accelerated and transient response A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis) Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis Gamma-secretase gene mutations in familial acne inversa An integrated approach to unravel hidradenitis suppurativa etiopathogenesis Hidradenitis suppurativa as an autoinflammatory keratinization disease Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases ASK1/2 signaling promotes inflammation in a mouse model of neutrophilic dermatosis Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6/SHP1) may contribute to neutrophilic dermatoses Spontaneous insertion of a b2 element in the ptpn6 gene drives a systemic autoinflammatory disease in mice resembling neutrophilic dermatosis in humans RIP1-driven autoinflammation targets IL-1alpha independently of inflammasomes and RIP3 An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis Ichthyosis molecular fingerprinting shows profound TH17 skewing and a unique barrier genomic signature Infliximab therapy for Netherton syndrome: A case report Generalized pustular psoriasis: clinical management and update on autoinflammatory aspects Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009 Cross-sectional survey on disease severity in Japanese patients with harlequin ichthyosis/ichthyosis: Syndromic forms and quality-of-life analysis in a subgroup Proteostasis control by the unfolded protein response CrossRef Full Text | Google Scholar Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond Keywords: autoinflammatory keratinization diseases keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome Citation: Takeichi T and Akiyama M (2020) KLICK Syndrome Linked to a POMP Mutation Has Features Suggestive of an Autoinflammatory Keratinization Disease Received: 22 August 2019; Accepted: 20 March 2020; Published: 30 April 2020 Copyright © 2020 Takeichi and Akiyama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Takuya Takeichi, dGFrZWljaGlAbWVkLm5hZ295YS11LmFjLmpw; Masashi Akiyama, bWFraXlhbWFAbWVkLm5hZ295YS11LmFjLmpw Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish A beautifully designed and affordable Xeon E rack server with room to grow and commendably low power usage The Fujitsu Primergy RX1330 M4 is ideal for SMEs that want a scalable Xeon E rack server and have an eye on the environment It offers a powerful hardware package at a great price while its smart internal design keeps energy consumption to an absolute minimum OS remote control requires Advanced license If you’re running an environment where storage density is a priority then the Fujitsu Server Primergy RX1330 M4 makes for a very strong choice While the LFF variant only has a conventional four-drive capacity the model we tested has eight SFF drive bays – and there’s another design with room for ten drives which is excellent for such a compact server All of that’s topped off with dual embedded M.2 slots which you can use to house your OS on a pair of SSDs (although you can’t use a pair of NVMe modules because one of the slots is SATA-only) Fujitsu’s microSD Enterprise card slips neatly into the motherboard’s internal USB 3 port and provides a VMware ESXi boot drive running off a mirrored pair of 64GB microSD cards Alongside these terrifically flexible storage options ranging from low-cost Celerons to the latest Xeon E-2200 models Our test system sports a speedy 3.4GHz six-core Xeon E-2236 which can be boosted right up to the CPU limit of 128GB A feature of Primergy servers that has always impressed us is their superb interior design Lift the lid off and you’ll find very little in the way of cable clutter combined with Fujitsu’s Cool-safe chassis design honeycomb air grilles and dedicated airflow channels means the five cooling fans in front of the CPU can run comparatively slowly which theoretically reduce power consumption and noise levels Our system came with dual hotplug 450W PSUs but in place of the second standard PSU you can specify a Fujitsu Integrated Battery Backup Unit (FJBU) It’s a smart alternative that obviates the need for a standalone UPS; 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There are sunbathing areas both on the ground floor and on the first floor. The total capacity is of 520 seats. We have 40 employees, including lifeguards and medical personnel,” the head of the Praid Salt Mine Tourism Service explained for Agerpres. According to the director of the Praid salt mine said a feasibility study has already been completed for the construction of a four-star hotel but that plans also include fitting out a camping area and the separation of the underground leisure area from that intended for patients who come here to treat various respiratory diseases The hotel will cost around EUR 15 million and funding will also come from European funds We use cookies for keeping our website reliable and secure providing social media features and to analyse how our website is used News | Crime Get our award-winning daily news email featuring exclusive stories I would like to be emailed about offers, event and updates from Evening Standard. Read our privacy notice An IT engineer who downloaded thousands of indecent images of children from the dark web and took hundreds of pictures using a hidden camera has been jailed for ten years National Crime Agency investigators arrested Daniel Praid outside his home in Biggleswade in Bedfordshire on March 27 last year and on a computer inside the property they found more than 300,000 indecent images and around 15,000 indecent films but in a set of files marked ‘personal’ and ‘peep’ they found a series of images taken by Praid himself using a hidden camera The pictures were taken in a variety of places but included images of women and girls getting changed and in the bathroom with one image showing how Praid had used a plastic cleaning fluid bottle to conceal his camera Other pictures showed Praid sexually assaulting an underage girl who he had befriended some years before Chat logs recovered from his hard drive revealed he had been sharing some of the indecent images online with other individuals Praid admitted 28 different charges including making and distributing indecent images of children At Birmingham Crown Court on Tuesday 15 March he was sentenced to ten years in prison Sick couple jailed after making indecent images of their own children Man arrested as children's summer camp shut down Metropolitan Police officer accused of possessing indecent image of NCA branch commander Paul Risby said: “We have identified and spoken to number of the victims of Praid’s voyeurism – they are all horrified at the violation of their privacy “Praid amassed hundreds of thousands of indecent images from the dark web some showing children being abused in the worst ways imaginable “His offending went one step further and involved him befriending and abusing a teenage girl “We are committed to tracking down offenders who use the internet to access and share this type of material wherever they are and bringing them to account.” Prince Louis steals the show at VE Day parade as he keeps dad William looking sharp and mimics brother George Prince Louis steals show with sweet antics at VE parade Ukraine 'launches stunning Kursk offensive' in major blow for Putin ahead of Victory Day celebrations Ukraine 'launches stunning Kursk offensive' in blow for Putin VE Day 2025 fashion: best looks from the day VE Day 2025 fashion: Princess of Wales to Lady Victoria Starmer UK tourists face major travel shake-up as Dubai airport set to close David Beckham’s 50th birthday bash in London 'shut down' by council over noise complaints David Beckham’s 50th birthday bash 'shut down' over noise complaints "Sofia Pride" 2024 is the biggest event in the protection of human rights in Bulgaria The focus of this year's edition is the role of LGBTI+ people in Bulgaria for the development of modern Bulgarian society The scene of "Sofia Pride" again gives young artists from the community the opportunity to perform and sing in front of thousands together with some of the biggest stars of Bulgarian music "Sofia Pride" is held for the 17th year in a row understanding of the community's problems is growing a large part of the problems of LGBTI+ people in Bulgaria remain unsolved Foremost among these is the legal regulation of same-sex partnerships which continues to be a focus in the work of those involved in community issues in the coming years transgender and intersex people (LGBTI) have always been part of society these groups have been subjected to various forms and degrees of oppression - from rejection by the people closest to them through religious stigmatization and pseudoscientific medicalization of "otherness" them Many forms of this oppression continue to exist today unnoticed by those who do not belong to any of these groups Pride's primary and short-term goal is to counteract the forces and mechanisms of this oppression and not simply by treating them equally regardless of their sexual orientation or gender identity but by accepting by society and improving the lives of people who live with all kinds of queer identities Pride has the potential to achieve this by raising the visibility of the otherwise obscured and marginalized bearers of these identities and thereby empowering them to be who they would feel happy to be as generated public debate and attacked the mechanisms of oppression expressed in prejudice and discrimination pride reveals the LGBTI communities as a legitimate part of society - Bulgarian voters and taxpayers who have the need and right to present their problems to the empowered and demand their resolution The necessary changes in state policy towards LGBTI minorities are within the competence of the legislative and executive powers Among them are recognition of the higher public danger of crimes committed on the basis of sexual orientation and gender identity or gender expression by introducing into the Penal Code qualified compositions for acts committed with such motives The organizers are fighting to strengthen the guarantees of protection against discrimination and protection against other violations of fundamental human rights through the signing and ratification by Bulgaria of Protocol No 16 to the European Convention for the Protection of Human Rights and Fundamental Freedoms They insist on effective prevention and fight against domestic and gender-based violence in relation to all victims without exception including victims in the families of same-sex couples as well as bringing Bulgarian legislation in line with the best international standards in this field clear and clearly articulated political declarations from the political parties represented in parliament condemning hate speech based on sexual orientation or gender identity and declaring a commitment to work together with vulnerable communities of LGBTI people on the problems and violations of fundamental rights of these communities documented by national and international human rights organizations Another struggle of Pride is the introduction of a clear maximally simplified and financially accessible administrative procedure for changing the civil sex by the civil status authorities as well as inclusion in the curricula of general education subjects in the school education system of current and scientific information concerning LGBTI people there was also a procession of the traditional Christian family Its participants see a threat to the traditional family not only in Sofia Pride or LGBT but also in the enormous consequences of industrialization which have had a crushing effect on the family in the West and in general in the entire post-industrial world More news from Bulgaria The last events from Turkey and some European cities made Romanians think about domestic holidays The online reservations portal HotelGuru.ro registered this year a growth in the number of accommodation options searches in the summer destinations Based on these searches, HotelGuru.ro made a list of the most appreciated beaches and swimming pools from Romania. The top of the most searched resorts include seaside resorts such as Mamaia or Eforie Nord, but also balneo resorts, such as Sovata, Praid and Baile Herculane. In June and July most of the Romanian tourists chose Mamaia resort Transylvania was also a chosen destination because of the swimming pools and SPA centers from this region Among the most popular destination from this year are the Praid swimming pool Colibita and the North West Termal Park from Satu Mare The main sports activities practiced by the tourists from Transylvania were cycling and mountain hiking, while the water sports lover chose rafting or  kayak. The accommodation in these area start from RON 60/person/night. the centre of the Salt Region in Transylvania the Praid Wellness Center reopens this week The year-round facility offers an extensive array of services to guests The newly opening Wellness Center offers a saltwater pool, a freshwater pool, a children’s pool, two jacuzzis and a sauna area for guests, Termál Online reports which is owned by the municipality of Praid It is mainly used to treat musculoskeletal and articular problems It was estimated at the time that the works would take two to three months meaning that even in the worst-case scenario they could reopen for the end-of-year holidays unexpected defects were found during the works There were also serious structural problems with some columns requiring structural reinforcement this was probably due to the fact that the saltwater had eroded many of the building elements over the years Promised to reopen in February at the beginning of the year The Wellness Center in Praid is opening again on Saturday “Indoor pools in spacious enclosed areas are open all year round for those who prefer a healthy lifestyle and those who want to recover,” the Wellness Center’s official website reads The spa’s greatest treasure is its thermal water which comes from a depth of 1,000 metres and is stored in a 10×20-metre pool The beneficial effects of the saltwater can be experienced by those suffering from musculoskeletal and joint problems but it is also recommended for skin diseases gynaecological problems and respiratory diseases you can find additional services in a spacious area of almost 1000 sqm: The recommended bathing time is 20-30 minutes which can be repeated 2-3 times with at least 20-minute breaks A full-price day ticket costs RON 120 (EUR 24) while a discounted day ticket costs RON 90 (EUR 18) and website in this browser for the next time I comment Y"},"category":false,"taxonomy":{"active":false,"name":"category"}},"markup":{"custom_html":true,"wpp-start":"","wpp-end":"<\/ul>","title-start":"","title-end":"<\/h2>","post-html":"{thumb} {title} {stats}<\/span>{excerpt}<\/p><\/li>"},"theme":{"name":""}} You have successfully joined our subscriber list SupportUs Newsletter © 2025 DailyNewsHungary | All rights reserved