Cottonstuart1925

Copyright © 2020 by S. Karger AG, Basel.Multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) is a rare disease caused by mutations in the X chromosomal PIGA gene. Clinically it is characterized by early-onset epilepsy, hypotonia, dysmorphic features, and variable congenital anomalies. PIGA codes for the phosphatidylinositol glycan-class A protein, which forms a subunit of an enzymatic complex involved in glycophosphatidylinositol (GPI) biosynthesis. We present a new case of MCAHS2 and perform a comprehensive review of the available literature to delineate the phenotypical traits associated with germline PIGA mutations. Furthermore, we provide functional evidence of pathogenicity of the novel missense mutation, c.154C>T; (p.His52Tyr), in the PIGA gene causative of MCAHS2 in our patient. By flow cytometry, we observed reduced expression of GPI-anchored surface proteins in patient granulocytes compared to control samples, proving GPI-biogenesis impairment. The patient's severe epilepsy with several daily attacks was refractory to treatment, but the frequency of seizures reduced temporarily under triple therapy with perampanel, rufinamide and vigabatrin. Our study delineates the known MCAHS2 phenotype and discusses challenges of diagnosis and clinical management in this complex, rare disease. Furthermore, we present a novel mutation with functional evidence of pathogenicity. Copyright © 2020 by S. read more Karger AG, Basel.Xia-Gibbs syndrome (XGS) is a rare neurological disorder characterized by global developmental delay, hypotonia, intellectual disability, seizures, and sleep apnea. XGS is defined by monoallelic pathogenic variants in AHDC1. In this study, we identified a Brazilian patient carrying a likely de novo AHDC1 nonsense mutation (c.451C>T; p.Arg151*) which was absent in both parents. All disease-causative variants already associated with XGS have been reviewed and the mutation described here corresponds to the closest one to the N-terminal region. Our findings were discussed based on the suggested genotype-phenotype correlation of the disease. Copyright © 2020 by S. Karger AG, Basel.The genetic basis for sporadic immunodeficiency in patients with 22q11.2 distal deletion syndrome is unknown. We report an adult with a type 1 (D-F) 22q11.2 distal deletion syndrome and recurrent severe infections due to herpes zoster virus, presenting mild T cell lymphopenia and diminished frequency of naive CD4 T cells to influenza, rotavirus, and SEB were conserved in the patient, but responses to tetanus toxoid were temporarily undetectable. Exomic sequencing identified the c.20_22dupCGG (NM_002745.4) variant in the remaining MAPK1 gene of the patient, which adds 1 alanine to the polyalanine amino-terminal tract of the protein (p.Ala7dup). The mother, unlike the father, was heterozygote for the variant. Western blot analysis with the patient's activated PBMCs showed a 91% reduction in the MAPK1 protein. Further studies will be necessary to determine whether or not the variant present in the remaining MAPK1 gene of the patient is pathogenic. Copyright © 2020 by S. Karger AG, Basel.The diagnosis of rare genetic diseases is one of the most difficult areas in medicine. Whole-exome sequencing (WES) technology makes it easier to diagnose these diseases. In addition, next-generation phenotyping can help to diagnose computer-based algorithms. Detailed dysmorphologic findings of 25 patients diagnosed by WES in our center were described. The success of this technology in diagnosing rare genetic diseases was investigated by scanning the photographs of 25 patients with Face2Gene application. The application listed possible preliminary diagnoses (30 disease suggestion). Of these, 12 (48%) cases were correctly matched. The most common disease group in the patients was neurological disease (96%). The most common mode of inheritance in the patients was autosomal recessive. The rate of consanguineous marriages was determined in 80% of the patients. Ten patients had microcephaly and 7 patients had corpus callosum anomaly. In our study, we found that the success of Face2Gene was lower than described in the literature. We think that the probable cause of this condition is that the cases are very rare, and there is not enough data about these diseases in the application. Therefore, it is recommended that applications should be used more frequently by pediatricians and clinical geneticists. The diagnosis of rare diseases still is quite difficult. Nowadays, WES is a successful method. However, applications such as Face2Gene help to make a clinical prediagnosis and create a larger database. Copyright © 2020 by S. Karger AG, Basel.An advanced protocol to prepare single extant and fossil pollen grains for transmission electron microscopy (TEM) analysis allows for the fast recovery of data on the ultrastructure of pollen/spores. The protocol is easy to apply and less time consuming than previous methods. The 'loss' of pollen grains and pollen that is 'difficult to locate' within the embedding material is avoided, and each single pollen grain can be prepared successfully for TEM analysis. This preparation method is meant as an addition to the single-grain method using combined light and scanning electron microscopy to investigate dispersed fossil pollen grains developed by Dr Reinhard Zetter in the late 1980s. © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Hemolysis represents an important source of error associated with the pre-analytical phase. Improving the protocols for detection, measurement, management of the parameters affected by the interference, and differentiation between hemolysis in vivo and in vitro, would favor a personalized management of hemolysis by increasing patient safety. For this, it is essential to agree on the definition of "hemolysis". From this definition, a critical point is to establish cut-offs of hemolysis management for each analyte studied in the clinical laboratory. Thus, in this review, the main methods described in the literature developed for obtaining a hemolysate are grouped, that simulate in controlled laboratory protocols what happens with a hemolyzed sample of a patient. These methods are grouped into 3 categories according to their basis of lysing cells freezing-thawing, osmotic shock and shear stress. In addition to development and improvement of methods for the study of hemolysis, it is necessary to carry out comparative studies to determine which one offers the best capabilities. Harmonization of the methods will allow to include them in working guidelines. All these strategies will allow to move from managing hemolysis on whole-sample basis to customize it analyte by analyte. The immunoassays methods need avoiding interferences that can influence result interpretation. Main sources of interference arise from either patient status, preparation and physiology or laboratory process and procedures. The aim of this non-systematic critical review is to highlight the preanalytical interferences on laboratory immunoassays. Blood hormone profile changes according with age and depending on sex these are important variables, mainly in newborn, during both sexual maturation and childbearing. Gonadotropins FSH and LH show a sharp increase with age in females, whereas in males LH appears rather stable. With age both males and females show progressive decay of the hormone profile. Stress causes variations, as it influences GH, prolactin, Cortisol and the total/free ratio of thyroid hormone. Diurnal variations, day of cycle, influence by estrogens on thyroid hormone are relevant for result variability. Paraproteins and autoantibodies can interfere in some assays particularly drug, vitamin D and thyroid hormone. As regards the variables due to sample matrix, and to evacuated tubes components, some additives and anticoagulants have been reported to influence specific assays, e.g. thyroid hormone. Hemolysis, lipemia and bilirubin cause interferences on specific techniques/tests, e.g. ferritin, TSH, Vitamin B12, progesterone and folic acid. Nicotine and cocaine addictions interfere with some hormones. Thus, laboratory professionals should be aware of preanalytical problems particularly important when dealing with the immunoassays, by taking appropriate actions to avoid any relevant interferences. Pseudothrombocytopenia by ethylenediaminetetraacetic acid (EDTA) is an infrequent phenomenon of in vitro platelet agglutination due to the presence of antiplatelet autoantibodies. It has no clinical significance, but misdiagnosis may lead to clinical or therapeutic decision-making. In this study we report a case of an 8-year-old boy with no history of platelet disorder presenting a low platelet count and a peripheral blood smear showing clumping of platelets by EDTA. The initial diagnosis hypothesis was of an idiopathic thrombocytopenic purpura, and an unnecessary bone marrow aspirate was made even though he did not have personal or family history of bleeding. A second sample collected in sodium citrate confirmed the pseudothrombocytopenia by EDTA. In conclusion, the laboratory should enhance a strong relationship with clinicians trying to avoid misunderstandings as that reflected in this case report. It should be reminded that, in those cases where a pseudothrombocytopenia by EDTA is suspected, a blood smear is mandatory to confirm platelet clumps and blood must be tested anticoagulated with another anticoagulant (i.e., sodium citrate or heparin). Urinalysis is one of the most important tests in the clinical laboratory. In this study we assessed the use of chemical preservative in urinalysis during preanalytical phase. Fifty first morning urine samples from medical laboratory patients were collected and stored with and without chemical preservative. Difference between medians were analyzed using Wilcoxon signed rank test for glucose, bilirubin, ketones, specific gravity, erythrocytes, pH, proteins, nitrites, leukocytes using urine strips; and on leukocytes, erythrocytes, epithelial cells, and bacteria in the urinary sediment, at 90 minutes after sampling. Our results showed that the specific gravity and the pH values increased in samples with chemical preservative in urine strip tests. Concerning urinary sediment analysis no differences were observed in the studied parameters between samples with and without chemical preservative. We suggest that the effect on urine pH is due to the chemical nature of the substances in the preservative. Thus, we caution about the use of chemical preservatives in samples to be analyzed within short time (i.e. less than 1.5 - 2 hours) after sample collection. Avoid chemical preservatives, in this situation, could help avoid changes in the pH and specific gravity, which could eventually help in maintaining quality in the preanalytical phase of urinalysis. Background and objective The analytes stability on serum and plasma are critical for clinical laboratory, especially if there is a delay in their processing or if they need to be stored for future research. The objective of this research was to determine the stability of K3EDTA-plasma and serum on different storage conditions. Materials and methods A total of thirty healthy adults were studied. The serum/plasma samples were centrifuged at 2000g for 10 minutes. Immediately after centrifugation, the serum/plasma analytes were assayed in primary tubes using a Cobas c501 analyzer (T0); the residual serum/plasma was stored at either 2-8°C or -20°C for 15 (T15) and 30 days (T30).Mean concentrations changes in respect of initial concentrations (T0) and the reference change values were calculated. For assessing statistical difference between samples, the Wilcoxon ranked-pairs test was applied. Results We evidenced instability for total bilirubin, uric acid, creatinine and glucose at T15 and T30 and stored at -20°C (p less then 0.