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Loricrin keratoderma is a rare early-onset autosomal dominant skin disorder. At present, no clinical reports have been published on characteristics of progressive aggravation and late-onset.To identified a new-found pedigree with c.323 GC mutation leading to progressive aggravation and late-onset loricrin keratoderma.Targeted next-generation sequencing of 267 genes associated with all skin abnormalities, sanger sequencing, and bioinformatics tools were used to identify the mutation in this new-found pedigree. Palm skin biopsy was used to observe the clinicopathological features of patient. Further, we constructed pcDNA3.1/V5-His-wild-LORICRIN, pcDNA3.1/V5-His-c.323GC-LORICRIN, and pcDNA3.1/V5-His-730insG-LORICRIN vectors, nucleofected into HaCaT strain to observe the subcellular localization of loricrin by using the laser scanning confocal microscopy.The proband and his affected father carried a heterozygous c.323 GC missense mutation (p.Gly108Ala) on LORICRIN. Bioinformatics analysis hinted that it had potential pathogenicity; the types of ligands, enzyme commission active sites, and the spatial structure of protein changed enormously. Laser scanning confocal microscopy showed that the signals from cells transfected with the pcDNA3.1/V5-His-730insG-LORICRIN vector were distributed mainly in the nucleus, whereas those from cells transfected with the pcDNA3.1/V5-His-c.323GC-LORICRIN vector were mainly located in the cytoplasm. Wild type loricrin was distributed in the nucleus and cytoplasm homogeneously CONCLUSION: The heterozygous c.323GC missense mutation on LORICRIN caused late-onset and progressive loricrin keratoderma in this large Chinese family. Our study revealed that a large number of loricrin gathered in the cytoplasm may disturb the normal proliferation and terminal differentiation of keratinocytes and lead to the late-onset loricrin keratoderma disease.

Background: The Chinese Government decided to quarantine Wuhan, the epicenter of the coronavirus disease-2019 (COVID-19) outbreak, on January 23, 2020, to contr

Background: The coronavirus disease-2019 (COVID-19) pandemic has affected more than 200 countries countries across the world, and most outbreaks have been a res

Extracellular glypicans play pivotal roles in organogenesis, stem cell maintenance and cancer development. However, the growth phenotypes associated with different levels of glypican are not consistent in development or tumorigenesis. This requires clarification on how the spatial patterns of glypican relate to the distribution of signaling molecules in different cellular contexts, and how glypican expression is regulated. We have previously reported that Dally, one of the glypican members in Drosophila, is required in the niche for the maintenance of germline stem cells (GSCs) via short-range BMP signaling in ovary. However, the regulatory mechanism of glypican pattern in the ovarian stem cell niche remains elusive. Our current data demonstrate that the Notch pathway is genetically upstream of Dally and its function to maintain GSCs relies on Dally expression. Combining yeast and fruit fly genetics, we illustrate that Dally is under the transcriptional control of Notch signaling via the transcription factor Su(H). Further, we assayed human glypicans and disease-associated variants in Drosophila ovary, which can serve as an effective system to evaluate the structure–function relationship of human homologs., Summary: Spatial regulation of a cell surface glycoprotein defines the territory of germline stem cells.

To understand the prevalence of overweight and obesity among adults of 5 monitoring areas in Guizhou Province and to analyze the correlation between overweight, obesity and incidence of related chronic diseases.Multistage stratified cluster random sampling was employed, using data from "the 2010- 2012 National Nutrition and Health Survey". The physical measurement and the TC, TG, HDLC and blood glucose were conducted among 3682 resident population aged 18 years and above who from 5 monitoring areas( Yunyan and Baiyun District, Dejiang, Qianxi andSansui County in Guizhou Province). To analyze the distribution of overweight, obesity and central obesity in the population and its relationship with diabetes, dyslipidemia and hypertension.The prevalence rates were 27%, 7. 5% and 16. 9% for overweight, obesity and the central obesity in 5 surveillance areas of Guizhou Provinc. The central obesity rate increase with age, which was the highest in the elderly( over 60years)( χ~2= 32. 03, P0. 001), the female were higher than the male( χ~2= 4. 2, P =0. 04). Under controlling for age, gender, regional factors, compared with the normal weight population, the onset risk of diabetes, hyperlipidemia and hypertension in the overweight populations were 1. 4 times, 1. 4 times and 2 times( 95% CI 1. 0- 2. 0, 1. 2-1. 7, 1. 6- 2. 5, P0. 05) respectively. The risk of obesity diabetes, hyperlipidemia and hypertension were 2. 6 times( 95% CI 1. 7- 4. 1, P0. 001), 1. 5 times( 95% CI 1. 1-1. 9, P0. 001) and 3. 7 times( 95% CI 2. 7- 5. 1, P0. 001), respectively. Central obesity may increase the risk of diabetes( OR = 2. 18, 95% CI 1. 58- 3. 01, P0. 001)and the risk of hypertension( OR = 2. 2, 95% CI 1. 74- 2. 57, P0. 001).Adult overweight and obesity were risk factors of diabetes, dyslipidemia and hypertension risk factors. Central obesity were risk factors of diabetes and hypertension risk factors.