43 research outputs found

    Expanding the clinical and mutational spectrum of B4GALT7-spondylodysplastic Ehlers-Danlos syndrome

    Get PDF
    Spondylodysplastic EDS (spEDS) is a rare connective tissue disorder that groups the phenotypes caused by biallelic B4GALT7, B3GALT6, and SLC39A13 mutations. In the 2017 EDS nosology, minimal criteria (general and gene-specific) for a clinical suspicion of spEDS have been proposed, but molecular analysis is required to reach a definite diagnosis. The majority of spEDS patients presented with short stature, skin hyperextensibility, facial dysmorphisms, peculiar radiological findings, muscle hypotonia and joint laxity and/or its complications. To date only 7 patients with β4GALT7-deficiency (spEDS-B4GALT7) have been described and their clinical data suggested that, in addition to short stature and muscle hypotonia, radioulnar synostosis, hypermetropia, and delayed cognitive development might be a hallmark of this specific type of spEDS. Additional 22 patients affected with an overlapping phenotype, i.e., Larsen of Reunion Island syndrome, all carrying a homozygous B4GALT7 mutation, are also recognized. Herein, we report on a 30-year-old Moroccan woman who fitted the minimal criteria to suspect spEDS, but lacked radioulnar synostosis and intellectual disability and presented with neurosensorial hearing loss and limb edema of lymphatic origin. Sanger sequencing of B4GALT7 was performed since the evaluation of the spEDS gene-specific minor criteria suggested this specific subtype. Mutational screening revealed the homozygous c.829G>T, p.Glu277* pathogenetic variant leading to aberrant splicing. Our findings expand both the clinical and mutational spectrum of this ultrarare connective tissue disorder. The comparison of the patient's features with those of the other spEDS and Larsen of Reunion Island syndrome patients reported up to now offers future perspectives for spEDS nosology and clinical research in this field

    Transcriptome-wide expression profiling in skin fibroblasts of patients with joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type

    Get PDF
    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients

    Episperm Separation from Walnut Kernels: Optimization of the Techniques and Impact on the Products Stability

    Get PDF
    Walnuts are characterized by the presence of a cuticle (episperm) that covers the kernels: although rich in fibers and antioxidants, it can negatively affect the derived products’ taste, color, and rheology. The aim of this study was to investigate its removal through a simple and efficient technique: by applying a process that does not damage the product and simultaneously ensuring good chemical profile and rheological stability of its derivatives, in particular of the paste. Different treatments were applied on the walnuts such as: roasting, blast chilling, soaking with different solutions (HCl, NaOH, NaHCO3, citric and ascorbic acid, at different concentrations), blanching (with pure water and NaHCO3 solutions), and steam blanching. The walnuts were then blown with compressed air to be peeled. Once individuated two optimal techniques, the treated walnuts were processed to obtain a paste that was chemically characterized and analyzed from a rheological point of view through both rotational and oscillatory modes (flow curves, amplitude and frequency sweep tests). The roasting and chilling treatments exhibited a positive impact on thermal expansion coefficients of seed and seed coat. The pre-treatments consisting only in the roasting and the soaking technique with 1% of baking soda (followed by a final roasting) gave the best peeling rates on kernels: both methods yield pastes that were chemically and rheologically stable. Further studies are needed to investigate how the peeling treatment may affect product taste and shelf-life

    Use of Vegetable Proteins for Stabilization of Hazelnut Paste

    Get PDF
    Plant proteins are attracting much interest as an ingredient in the food sector due to their functional properties. These products are, in fact, widely studied to improve the quality of food products and to develop new types of bio packaging. This paper aims to study and investigate the potential of adding vegetable proteins (specifically soybean and sunflower) to improve the physicochemical stability of hazelnut pastes which are widely used in the food sector as a product itself or as an ingredient for many products, such as pastry, confectionery, and ice-cream. To investigate the effect of protein incorporation, hazelnut paste samples were stored under temperature accelerated conditions to simulate at least 10 months of shelf-life under normal storage conditions, and periodically analyzed for water activity, lipid oxidation, tocopherols content and oil separation. The study showed promising results for both added proteins, especially in terms of the physical stabilization of the product

    Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes

    Get PDF
    To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS). Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex- and age-adjusted normative reference values. Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS ≥4 and <7) in 8 patients and severe (NRS ≥7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type. SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS

    Emotional dissonance and exhaustion among healthcare professionals: the role of the perceived quality of care

    Get PDF
    Objectives The aim of this exploratory study was to analyze the association between emotional dissonance and emotional exhaustion among healthcare professionals, and the mediating role of the perceived quality of care in this relationship. Material and Methods Self-report questionnaires were administered to 724 healthcare workers. The measurement model was tested and the mediation hypothesis was verified through hierarchical multiple regression analyses. Bootstrapping was used to construct confidence intervals to evaluate the mediation effects. Results Emotional dissonance was significantly related to emotional exhaustion, and the perceived quality of care was negatively related to emotional exhaustion. The perceived quality of care had a partial mediating effect on the relationship between emotional dissonance and emotional exhaustion. Emotional dissonance had a significant effect on emotional exhaustion, and the perceived quality of care was a mediating factor in this relationship among healthcare professionals. Conclusions The management of the perceived quality of care may be helpful in the prevention of burnout and distress in the workplace. Int J Occup Med Environ Health. 2019;32(6):841–5

    Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3

    Get PDF
    : Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the "segmentation clock" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c.822-5C>T) or compound heterozygous (c.[863dup];[1063G>A]) and (c.[521G>T];[890T>G]) variants in LFNG. Notably, the c.822-5C>T change, affecting the polypyrimidine tract of intron 5, is the first non-coding variant reported in LFNG. This study further refines the clinical and molecular features of spondylocostal dysostosis 3 and adds to the numerous investigations supporting the usefulness of trio-ES approach in prenatal and neonatal settings

    Koolen-de Vries Syndrome: Clinical Report of an Adult and Literature Review

    No full text
    Koolen-de Vries syndrome (KdS) is a rare genetic condition characterized by typical facial dysmorphisms, cardiac and renal defects, skeletal anomalies, developmental delay, and intellectual disability of variable level. It is caused by a 440-680-kb deletion in the 17q21.31 region, encompassing CRHR1, MAPT, IMP5, STH, and KANSL1, or by an intragenic KANSL1 mutation. The majority of the patients reported are pediatric or young adults, and long-term studies able to define the prognosis of the disease are lacking. Here, we report a patient in the fourth decade misdiagnosed in the past as classical Ehlers-Danlos syndrome for the presence of generalized joint hypermobility, who carried a 546-kb deletion in 17q21.31, and compare his phenotype with those of the few KdS adults (aged >18 years) described so far. We observed a favorable prognosis of epilepsy and cardiovascular signs and reduction of joint hypermobility with age, thus providing insight into the natural history of the disorder

    A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed by molecular testing

    No full text
    The 2017 EDS revised nosology indicates that minimal criteria suggestive for classical Ehlers-Danlos syndrome (cEDS) are skin hyperextensibility plus atrophic scarring together with either generalized joint hypermobility (gJHM) and/or at least three minor criteria that include cutaneous features and gJHM complications. Confirmatory molecular testing is obligatory to reach a final diagnosis. Although the large majority of the patients presents with these clinical features, some do not and might remain undiagnosed or misdiagnosed. Here we describe a family with 2 affected members, a 23-year-old proposita and her 51-year-old mother, who presented subtle cutaneous signs, including a variable degree of skin hyperextensibility without extensive widened atrophic scars that apparently better fitted with the overlapping hypermobile EDS. The proposita also presented gastrointestinal symptoms secondary to aberrant mast cells mediators release, making the clinical picture even more puzzling. Both patients were diagnosed by molecular testing that revealed a COL5A1 splice mutation. This report highlights the relevance of molecular analysis in patients presenting rather mild signs of EDS, especially in familial cases, and the importance of clinical expertise to make such a diagnosis
    corecore