Orbital Edema Secondary to a Sphenoidal Mass as the Presenting Symptom of High-Risk Precursor B-Cell Acute Lymphoblastic Leukemia

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, known to present with ocular manifestations in rare cases. Case Presentation: We describe the case of a 9-year-old previously healthy male who developed a 2-day history of periocular swelling and was found on MRI to have a large sphenoidal mass. Further work up showed involvement of the spinal cord, iliac crests, and kidneys. His initial blood work showed no hematological abnormalities. A bone marrow biopsy taken from the iliac crest demonstrated >90% B lymphoblasts and flow cytometry was positive for CD19. Overall, his investigations were consistent with a diagnosis of precursor B-cell ALL (pre B-ALL). His neuro-ophthalmic exam showed right-sided subtle periocular edema, decreased palpebral fissure height, and proptosis. Posterior exam showed mild nasal elevation of the right optic disc without vessel obscuration and mild tortuosity of the peripheral vessels. He otherwise had no overt signs of afferent or efferent dysfunction despite the proximity of the mass to his optic nerve and globe. Conclusion: This case demonstrates that high-risk pre B-ALL, a childhood cancer not commonly associated with orbital manifestations, can present with orbital edema and normal leukocyte count in an otherwise healthy child

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

Endoscopic goniotomy: Early clinical experience in congenital glaucoma

Purpose: To review the technique and early outcomes of endoscopic goniotomy (EG) in children with opaque corneas and primary congenital glaucoma (PCG) or developmental glaucoma with ocular or systemic anomalies (DG).Methods: EG was performed for approximately 300 degrees of the angle through temporal and superonasal corneal incisions. We retrospectively reviewed consecutive cases from 2003 to 2007. Primary outcome was intraocular pressure (IOP) change from baseline to last postoperative visit. Success was defined as IOP \u3c or=21 mm Hg with or without medication but no further surgical intervention.Results: Fourteen eyes of 8 patients (4 PCG, 4 DG) were included. Mean age at surgery was 3.88+/-3.72 months. The reduction in IOP from baseline to the last follow-up visit was -16.7+/-16.7 mm Hg. Success was achieved in 6 of the 16 eyes (Total=43%, PCG=50%, DG=30%). Corneal diameter and axial length remained stable in all eyes. Two patients with DG needed additional surgery after 8 to 9 months. Complications included cataract and zonular dialysis both in 2 patients with aniridia.Conclusions: This pilot study indicates that EG shows reasonable potential for IOP control in congenital glaucoma. The safety and efficacy of EG needs to be further studied with a larger sample size and comparison to other angle surgery techniques

Disc excavation in dominant optic atrophy: Differentiation from normal tension glaucoma

Objective: In patients with dominant optic atrophy (DOA, Kjer type), excavation of the optic nerve develops, and these patients may be misdiagnosed as having normal tension glaucoma (NTG). This study examined disc morphologic features in patients with DOA and explored features that help distinguish this condition from NTG.Design: Noncomparative, observational case series.Participants: Patients with DOA who were seen at the Duke University Eye Center between 1987 and 1996 and who had bilateral optic nerve photographs.Methods: Retrospective chart review of the results of visual acuity testing, visual field testing by Goldmann perimetry, color vision testing, intraocular pressure measurement, and observation of bilateral optic nerve photographs.Main outcome measures: Appearance of the optic disc and peripapillary zone in patients with DOA.Results: Nine patients were identified. The mean age at the time of evaluation was 28 years (range, 11-62 years). Most patients had a mild to moderate reduction in visual acuity. Color vision as tested with Hardy-Rand-Rittler plates was reduced (4.0/10 +/- 4.2/10). A cup-to-disc ratio of more than 0.5 was observed in at least one eye of eight patients. A temporal wedge-shaped area of excavation was observed in 14 of the 18 eyes studied. Moderate to severe temporal pallor was observed in all of the eyes. Pallor of the remaining (noncupped) neuroretinal rim was also observed consistently, ranging from mild to moderate. A gray crescent and some degree of peripapillary atrophy were noted in all eyes.Conclusions: Several clinical features, including early age of onset, preferential loss of central vision, sparing of the peripheral fields, pallor of the remaining neuroretinal rim, and a family history of unexplained visual loss or optic atrophy, help to distinguish patients with DOA from those with NTG

SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope.

Changes in the transcriptional state of genes have been correlated with their repositioning within the nuclear space. Tethering reporter genes to the nuclear envelope alone can impose repression and recent reports have shown that, after activation, certain genes can also be found closer to the nuclear periphery. The molecular mechanisms underlying these phenomena have remained elusive. Here, with the use of dynamic three-dimensional tracking of a single locus in live yeast (Saccharomyces cerevisiae) cells, we show that the activation of GAL genes (GAL7, GAL10 and GAL1) leads to a confinement in dynamic motility. We demonstrate that the GAL locus is subject to sub-diffusive movement, which after activation can become constrained to a two-dimensional sliding motion along the nuclear envelope. RNA-fluorescence in situ hybridization analysis after activation reveals a higher transcriptional activity for the peripherally constrained GAL genes than for loci remaining intranuclear. This confinement was mediated by Sus1 and Ada2, members of the SAGA histone acetyltransferase complex, and Sac3, a messenger RNA export factor, physically linking the activated GAL genes to the nuclear-pore-complex component Nup1. Deleting ADA2 or NUP1 abrogates perinuclear GAL confinement without affecting GAL1 transcription. Accordingly, transcriptional activation is necessary but not sufficient for the confinement of GAL genes at the nuclear periphery. The observed real-time dynamic mooring of active GAL genes to the inner side of the nuclear pore complex is in accordance with the 'gene gating' hypothesis

OZCAR : The French Network of Critical Zone Observatories

[Departement_IRSTEA]Eaux [TR1_IRSTEA]ARCEAU [ADD1_IRSTEA]Hydrosystèmes et risques naturels [Departement_IRSTEA]Eaux [TR1_IRSTEA]ARCEAU [ADD1_IRSTEA]Hydrosystèmes et risques naturelsSpecial Section: Hydrological ObservatoriesInternational audienceThe French critical zone initiative, called OZCAR (Observatoires de la Zone Critique-Application et Recherche or Critical Zone Observatories-Application and Research) is a National Research Infrastructure (RI). OZCAR-RI is a network of instrumented sites, bringing together 21 pre-existing research observatories monitoring different compartments of the zone situated between "the rock and the sky," the Earth's skin or critical zone (CZ), over the long term. These observatories are regionally based and have specific initial scientific questions, monitoring strategies, databases, and modeling activities. The diversity of OZCAR-RI observatories and sites is well representative of the heterogeneity of the CZ and of the scientific communities studying it. Despite this diversity, all OZCAR-RI sites share a main overarching mandate, which is to monitor, understand, and predict ("earthcast") the fluxes of water and matter of the Earth's near surface and how they will change in response to the "new climatic regime." The vision for OZCAR strategic development aims at designing an open infrastructure, building a national CZ community able to share a systemic representation of the CZ , and educating a new generation of scientists more apt to tackle the wicked problem of the Anthropocene. OZCAR articulates around: (i) a set of common scientific questions and cross-cutting scientific activities using the wealth of OZCAR-RI observatories, (ii) an ambitious instrumental development program, and (iii) a better interaction between data and models to integrate the different time and spatial scales. Internationally, OZCAR-RI aims at strengthening the CZ community by providing a model of organization for pre-existing observatories and by offering CZ instrumented sites. OZCAR is one of two French mirrors of the European Strategy Forum on Research Infrastructure (eLTER-ESFRI) project