Kälviän maankäytön kehityskuva:”asu lähellä, näe kauas”: kuntasuunnittelun kurssi ja erikoiskurssi 2013

Sisällys Helka-Liisa Hentilä: Johdanto Tiina Pyhäluoto: Kurssin kuvaus Tiia Possakka: Kälviän kehityshistoriallinen analyysi Laura Felin: Kaavoituksella määritellään tulevaisuuden kehityssuunnat - Kälviän kaavoitushistoria Kirsi Översti: Taajamakuvallisen kartoituksen käytännöt Katariina Huikari: Taajamakuvallisen kartoituksen menetelmät Henry Tossava: Kälviän taajamakuva Henrikki Moisander: Kälviän kirkonkylä ja alueidenkäytön ohjaaminen kuntatasolla Risto Honkonen: Kälviän kirkonkylä ja alueidenkäytön strateginen ohjaaminen Keski-Pohjanmaan maakunnassa Karri Hakala ja Ilona Heikkinen: Kälviän asukaskysely: ”Pieni ja kotoisa kylä lähellä kaupunkia” Liite: Strategiateksti ja suunnit elmaplanssi

A novel frameshift variant in CEP78 associated with nonsyndromic retinitis pigmentosa, and a review of CEP78-related phenotypes

Abstract Background: Pathogenic variants in the CEP78 gene can present as atypical Usher syndrome or as retinitis pigmentosa. Here, we present a review of all reported cases of CEP78 variants in the literature to date and present a novel variant of CEP78, c.1261_1262delinsA, in a consanguineous northern Finnish family with two individuals. Materials and methods: Our patients were first discovered in a registry-based study. Later, they gave their written consent for this study. In order to describe the genotype and phenotype, their historic clinical patient data and genetic data were gathered, and a clinical ophthalmic examination and an audiogram were performed. For this review, a PubMed search using the keyword CEP78 was carried out. The first article on CEP78 was published in the year 2007, and the publications from the years 2007–2021 were included. Results: A large gene panel identified a homozygous CEP78 c.1261_1262delinsA variant in two affected siblings. In addition to the classical signs of retinitis pigmentosa, both siblings had large round atrophic spots in the mid periphery, and hyperautofluorescence of the macula. Patient 1 had age-related hearing impairment; patient 2 had normal hearing. In total, 20 articles have been published about CEP78. Eight of these papers report patient data with the affected individuals typically having retinal dystrophy combined with sensorineural hearing impairment, classified as atypical Usher syndrome. Conclusions: Here, we present a comprehensive review of CEP78 and expand the knowledge of pathogenic CEP78 variants and the phenotypic variety

Inflammation and neutrophil oxidative burst in a family with NFKB1 p.R157X LOF and sterile necrotizing fasciitis

Abstract Loss-of-function (LOF) mutations in NFKB1, coding for p105, may cause common variable immunodeficiency due to dysregulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κΒ) pathway. Monoallelic LOF variants of NFKB1 can predispose to uncontrolled inflammation including sterile necrotizing fasciitis or pyoderma gangrenosum. In this study, we explored the impact of a heterozygous NFKB1 c.C936T/p.R157X LOF variant on immunity in sterile fasciitis patients and their family members. The p50 or p105 protein levels were reduced in all variant carriers. Interleukin-1β (IL-1β) and interleukin-8 (IL-8) levels were elevated in vitro, potentially contributing to the very high neutrophil counts observed during fasciitis episodes. Phosphorylation of p65/RelA was reduced in p.R157X neutrophils suggesting defective activation of canonical NF-κB. Oxidative burst after NF-κB-independent phorbol 12-myristate 13-acetate (PMA) stimulation was similar in both p.R157X and control neutrophils. Comparable amounts of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex subunits were found in p.R157X and control neutrophils. However, a compromised oxidative burst was observed in p.R157X neutrophils following activation of NF-κB-dependent mechanisms following stimulation of toll-like receptor 2 (TLR2) and Dectin-1. Neutrophil extracellular trap formation was not affected by p.R157X. In summary, the NFKB1 c.C936T/p.R157X LOF variant has an impact on inflammation and neutrophil function and may play a role in the pathogenesis of sterile necrotizing fasciitis