Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

Background: As the SARS-CoV-2 Omicron variant emerged and spread globally at an alarming speed, healthcare workers’ (HCWs) uncertainties, worries, resilience, and coping strategies warranted assessment. The COVID-19 pandemic had a severe psychological impact on HCWs, including the development of Post-Traumatic Stress symptoms. Specific subgroups of HCWs, such as front-line and female workers, were more prone to poor mental health outcomes and difficulties facing stress. Methods: The responses to an online questionnaire among HCWs in the Kingdom of Saudi Arabia (KSA) were collected from 1 December 2021 to 6 December 2021, aiming to assess their uncertainties, worries, resilience, and coping strategies regarding the Omicron variant. Three validated instruments were used to achieve the study’s goals: the Brief Resilient Coping Scale (BRCS), the Standard Stress Scale (SSS), and the Intolerance of Uncertainty Scale (IUS)—Short Form. Results: The online survey was completed by 1285 HCWs. Females made up the majority of the participants (64%). A total of 1285 HCW’s completed the online survey from all regions in KSA. Resilient coping scored by the BRCS was negatively and significantly correlated with stress as scored by the SSS (r = −0.313, p < 0.010). Moreover, intolerance of uncertainty scored by the IUS positively and significantly correlated with stress (r = 0.326, p < 0.010). Increased stress levels were linked to a considerable drop in resilient coping scores. Furthermore, being a Saudi HCW or a nurse was linked to a significant reduction in resilient coping ratings. Coping by following healthcare authorities’ preventative instructions and using the WHO website as a source of information was linked to a considerable rise in resilient coping. Conclusions: The negative association between resilient coping and stress was clearly shown, as well as how underlying intolerance of uncertainty is linked to higher stress among HCWs quickly following the development of a new infectious threat. The study provides early insights into developing and promoting coping strategies for emerging SARS-CoV-2 variants.

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STING-associated vasculopathy of infantile-onset (SAVI) is one of the newly identified types of interferonopathies. SAVI is caused by heterozygous gain-of-function mutations in the STING1. We herein report for the first time a homozygous variant in the STING1 gene in two siblings that resulted in constitutive activation of STING gene and the SAVI phenotype. Exome sequencing revealed a novel homozygous NM_198282.3: c.841C&gt;T; p.(Arg281Trp) variant in exon 7 of the STING1 gene. The variant segregated in the family to be homozygous in all affected and either heterozygous or wild type in all healthy. Computational structural analysis of the mutants revealed changes in the STING protein structure/function. Elevated serum beta-interferon levels were observed in the patients compared to the control family members. Treatment with Janus kinase inhibitor (JAK-I) Ruxolitinib suppressed the inflammatory process, decreased beta-interferon levels, and stopped the progression of the disease.