In this study, we analyzed full-length SARS-CoV-2 genomes from multiple countries to determine early trends in the evolutionary dynamics of the novel COVID-19 pandemic. Results indicated SARS-CoV-2 ...evolved early into at least three phylogenetic groups, characterized by positive selection at specific residues of the accessory proteins ORF3a and ORF8. Also, we are reporting potential relevant sites under positive selection at specific sites of non-structural proteins nsp6 and helicase. Our analysis of co-evolution showed evidence of epistatic interactions among sites in the genome that may be important in the generation of variants adapted to humans. These observations might impact not only public health but also suggest that more studies are needed to understand the genetic mechanisms that may affect the development of therapeutic and preventive tools, like antivirals and vaccines. Collectively, our results highlight the identification of ongoing selection even in a scenario of conserved sequences collected over the first 3 months of this pandemic.
Although neuroblastoma is one of the most common extra-cranial tumors in the pediatric population, it is rarely seen as a metastasis to the mandibular bone. The following is a case report of a ...3-year-old male who initially presented with a submandibular mass that was proven to be a poorly differentiated metastatic neuroblastoma through excisional biopsy. This report is one of the few case reports that demonstrates metastatic submandibular neuroblastoma with mandibular bone involvement in the pediatric population.
SATB2-associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial ...anomalies. Previous studies have largely been restricted to case reports and small series without in-depth phenotypic characterization or genotype-phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals with a molecularly confirmed diagnosis of SAS were referred after clinical diagnostic testing. In this series we present the most comprehensive phenotypic and genotypic characterization of SAS to date, including prevalence of each clinical feature, neurodevelopmental milestones, and when available, patient management. We confirm that the most distinctive features are neurodevelopmental delay with invariably severely limited speech, abnormalities of the palate (cleft or high-arched), dental anomalies (crowding, macrodontia, abnormal shape), and behavioral issues with or without bone or brain anomalies. This comprehensive clinical characterization will help clinicians with the diagnosis, counseling and management of SAS and help provide families with anticipatory guidance.
Groundwater quality is of great importance in the US to protect public health. In Gaston County, North Carolina, more than 8,000 households use private wells for their drinking water supplies. The ...county's 220,000 inhabitants face economic challenges with a median household income lower than the neighboring city of Charlotte. The Gaston County Department of Health and Human Services (GCDHHS) implements and enforces state rules and regulations on private wells. Its environmental health staff issue permits for the construction of private wells, ensure well drillers are licensed, inspect wells before issuing certificates of completion, collect water samples for mandatory testing, and assure that wells are repaired and abandoned properly. The collaborators will continue to create maps of private wells and display them on the GCDHHS Web site. A data layer in the website will include well attributes such as depth, flow, static water level, type of casing, name of well driller, and test results for well water. Information will be accessible to the public and GCDHHS environmental health staff working in the field.
While X-linked intellectual disability (XLID) syndromes pose a diagnostic challenge for clinicians, an increasing number of recognized disorders and their genetic etiologies are providing answers for ...patients and their families. The availability of clinical exome sequencing is broadening the ability to identify mutations in genes previously unrecognized as causing XLID. In recent years, the IQSEC2 gene, located at Xp11.22, has emerged as the cause of multiple cases of both nonsyndromic and syndromic XLID. Herein we present a case series of six individuals (five males, one female) with intellectual disability and seizures found to have alterations in IQSEC2. In all cases, the diagnostic odyssey was extensive and expensive, often including invasive testing such as muscle biopsies, before ultimately reaching the diagnosis. We report these cases to demonstrate the exhaustive work-up prior to finding the changes in IQSEC2 gene, recommend that this gene be considered earlier in the diagnostic evaluation of individuals with global developmental delay, microcephaly, and severe, intractable epilepsy, and support the use of intellectual disability panels including IQSEC2 in the first-line evaluation of these patients.
Although most cases of coccidioidomycosis are subclinical or self-limited respiratory disease, 1% lead to extrathoracic dissemination and become fatal, especially in patients with an associated ...immunodeficiency. Up to 30%-50% of patients with defects in cell-mediated immunity, those with AIDS and recipients of solid-organ transplants, may develop disseminated coccidioidomycosis (DC). Within the primary immunodeficiencies, an uncommon group is caused by C-terminal NFKB2 pathogenic variants.
We performed a literature search of core databases. Written informed consent for the study and for publication was obtained.
A 7-year-old Mexican girl, eldest of 3 sisters, no relevant family history, and a history of recurrent upper respiratory infections and alopecia totalis was admitted with DC involving pulmonary, soft tissue, skin, bone and joint compromise. The immunodeficiency assessment showed low IgM and NK cells. We found an NFKB2 de novo heterozygous nonsense mutation of c.2611C>T (p.Gln871*). She was treated with liposomal amphotericin B and itraconazole with surgical debridement. The clinical phenotype of this primary immunodeficiency is characterized by antibody deficiency and associated broncho-pulmonary predisposition to infection, but moreover also opportunistic infections and autoimmunity, most recognizable alopecia and adrenocorticotropic hormone-deficiency. After 1 year of her discharge, she continues under surveillance with antifungal therapy with itraconazole and replacement intravenous immunoglobulin until today.
This is the first case report of DC in a patient with an NFKB2 pathogenic variant and it illustrates the importance of screening for primary immunodeficiencies in patients with disseminated fungal infections.
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