Pathogenic STX3 variants affecting the retinal and intestinal transcripts cause an early-onset severe retinal dystrophy in microvillus inclusion disease subjects

Biallelic STX3 variants were previously reported in five individuals with the severe congenital enteropathy, microvillus inclusion disease (MVID). Here, we provide a significant extension of the phenotypic spectrum caused by STX3 variants. We report ten individuals of diverse geographic origin with biallelic STX3 loss-of-function variants, identified through exome sequencing, single-nucleotide polymorphism array-based homozygosity mapping, and international collaboration. The evaluated individuals all presented with MVID. Eight individuals also displayed early-onset severe retinal dystrophy, i.e., syndromic—intestinal and retinal—disease. These individuals harbored STX3 variants that affected both the retinal and intestinal STX3 transcripts, whereas STX3 variants affected only the intestinal transcript in individuals with solitary MVID. That STX3 is essential for retinal photoreceptor survival was confirmed by the creation of a rod photoreceptor-specific STX3 knockout mouse model which revealed a time-dependent reduction in the number of rod photoreceptors, thinning of the outer nuclear layer, and the eventual loss of both rod and cone photoreceptors. Together, our results provide a link between STX3 loss-of-function variants and a human retinal dystrophy. Depending on the genomic site of a human loss-of-function STX3 variant, it can cause MVID, the novel intestinal-retinal syndrome reported here or, hypothetically, an isolated retinal dystrophy

Durability assessment of the Alaçatı tuff (Izmir) in western Turkey

Ala double dagger atA +/- tuff has been used extensively as a source of building stone for outdoor and indoor decorations since the historical times in and around the tourist town of Ala double dagger atA +/- (western Turkey). The use of the Alacati tuff in buildings has been made compulsory by the Ala double dagger atA +/- municipality, for preserving the historical appearance of the buildings, after 2005 in Ala double dagger atA +/-. It has been noticed that, evident deteriorations developed in tuff surfaces of the stone buildings and garden walls within 5-6 years of their emplacement. Durability properties of the Ala double dagger atA +/- tuff are evaluated by determining the mineralogical, chemical, and physico-mechanical properties of the fresh tuff samples obtained from the only operative quarry in the area. Ageing tests such as Na2SO4 and MgSO4 salt crystallization, freezing-thawing, and wetting-drying were conducted on the fresh tuff samples to assess their durability. Additionally, the durability of the tuff is also evaluated by determining its average pore diameter, saturation coefficient, wet-to-dry strength ratio, static rock and slake-durability indices. Fresh Ala double dagger atA +/- tuff has high porosity and low unit weight and strengths and are classified to be very poor to moderately durable stone based on the test results of different durability assessment methods. Mineralogical and geochemical analyses have also been carried out on the deteriorated tuff samples collected from the surfaces of the stone buildings to determine the effect of weathering on tuff and the test results have been compared with those of the fresh tuff samples. There is no major difference observed between the mineralogy and chemistry of the fresh and weathered tuff samples thus, it has been concluded that physical weathering has been dominant in the area in deterioration of tuff