Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: a novel whole exome sequencing approach. | LitMetric
Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Physiopathology and Transplantation, Università degli Studi di Milano Via Pace 9, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. Electronic address:
Published: July 2020
AI Article Synopsis
Article Abstract
Background: Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients.
Objective: To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases.
Methods: Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease.
Results: WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL.
Conclusion: Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged.
The annotated and predicted genomes of five archaeal strains (AS1, AS2, AS8, AS11 and AS19), isolated from Sfax solar saltern sediments (Tunisia) and affiliated with , were performed by RAST webserver (Rapid Annotation using Subsystem Technology) and NCBI prokaryotic genome annotation pipeline (PGAP). The results showed the ability of strains to use a reduced semi-phosphorylative Entner-Doudoroff pathway for glucose degradation and an Embden-Meyerhof one for gluconeogenesis. They could use glucose, fructose, glycerol, and acetate as sole source of carbon and energy.
Background: Micronutrient research on Graves' disease (GD) is limited and controversial. Therefore, in order to explore possible correlations between genetically predicted amounts of six micronutrients [Copper (Cu), Iron (Ir), Zinc (Zn), Calcium (Ca), Vitamin C (VC), and Vitamin D (VD)] and GD risk, we carried out Mendelian randomization research (MR).
Methods: We conducted an MR analysis using genome-wide association studies (GWAS) from people of European ancestry and aggregated information from UK Biobank to provide insight into the relationships between micronutrients and GD.
We present the case of a previously healthy 11-year-old boy who developed hepatitis in the setting of regular intake of Apetamin. Apetamin is an appetite stimulant not approved by the United States Food and Drug Administration that contains cyproheptadine, lysine, and multiple B vitamins. It is illegally imported into the United States and can be purchased online.
Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
Background: Elevated levels of atmospheric pollutants might disrupt the metabolism of vitamin D in the skin. Studies showed inconsistent results about the impact of air pollution on the serum vitamin D level. This study aims to systematically review the influence of air pollution on vitamin D levels.
