Expanding the phenotypic spectrum of truncating POGZ mutations: Association with CNS malformations, skeletal abnormalities, and distinctive facial dysmorphism

Exome sequencing has led to the comprehension of the molecular bases of several forms of neurodevelopmental disorders, a clinically heterogeneous group of diseases characterized by intellectual disability (ID) and autism spectrum disorder (ASD). De novo mutations in POGZ has been causally linked to isolated ASD and syndromic ID, only recently. Here we report on a 15 year-old girl in whom exome sequencing allowed to identify a de novo POGZ truncating mutation as the molecular cause underlying a complex phenotype apparently not fitting any recognized syndrome. We describe the evolution of her clinical features with age, and review published clinical data of patients with POGZ mutations to systematically analyze the clinical spectrum associated with mutations. Our finding expands the clinical and molecular spectrum of POGZ mutations. Revision of the literature indicate that moderate to severe ID, microcephaly, variable CNS malformations, reduced growth, brachytelephalangy, and facial dysmorphism represent recurrent features associated with POGZ mutations.

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Acne conglobata in a long-term survivor with trisomy 13, accompanied by selective IgM deficiency

Trisomy 13 (T13) is a congenital chromosomal disorder that is usually fatal within 2 years of birth, and only a few patients have been reported to reach adolescence. Here, we report a male long-term survivor of T13, currently 15 years of age, with a several-year history of extensive acne conglobata (AC) with abscesses on the face and neck. Methicillin-resistant Staphylococcus aureus was consistently isolated from the pustular lesions. Serum IgM levels were extremely low at 10 mg/dl. There were no abnormalities in neutrophil and total B cell number, or in serum IgA and IgG levels. Increased CD8+ T cell counts and inversion of the CD4/CD8 ratio were observed repeatedly. The patient's clinical features and laboratory data support a diagnosis of selective IgM deficiency (SIgMD) with concurrent AC. Immunoglobulin replacement therapy elevated serum IgM levels to the normal range and reduced the severity of AC. We suggest that T13 may represent a syndromic disorder associated with multiple organ malformation and a risk of developing immunodeficiency involving SIgMD. Because pediatric SIgMD is rare and an immunological abnormality in T13 patients has not previously been reported, we describe the patient's clinical course.

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Paroxysmal theta power reactivity is related to survival in anoxic vegetative state patients

Disorders of consciousness (DOC) due to severe acute brain injuries (e.g., anoxic encephalopathy) are defined by loss of consciousness and absence of reactivity to external stimuli. DOC patients are often classified as being in a state of coma, a vegetative state (VS) or a minimally consciousness state (MCS) (Schorr et al., 2015). A shift in awareness from VS to MCS includes clinically-defined behaviors such as visual fixation, directed reaction to stimuli, and congruent emotional responses. However, these cognitively mediated behaviors appear inconsistently, making it difficult to reliably identify them as non-reflexive behaviors (Fingelkurts et al., 2011).

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Enhanced air dispersion modelling at a typical Chinese nuclear power plant site: Coupling RIMPUFF with two advanced diagnostic wind models

Publication date: September 2017
Source:Journal of Environmental Radioactivity, Volumes 175–176
Author(s): Yun Liu, Hong Li, Sida Sun, Sheng Fang
An enhanced air dispersion modelling scheme is proposed to cope with the building layout and complex terrain of a typical Chinese nuclear power plant (NPP) site. In this modelling, the California Meteorological Model (CALMET) and the Stationary Wind Fit and Turbulence (SWIFT) are coupled with the Risø Mesoscale PUFF model (RIMPUFF) for refined wind field calculation. The near-field diffusion coefficient correction scheme of the Atmospheric Relative Concentrations in the Building Wakes Computer Code (ARCON96) is adopted to characterize dispersion in building arrays. The proposed method is evaluated by a wind tunnel experiment that replicates the typical Chinese NPP site. For both wind speed/direction and air concentration, the enhanced modelling predictions agree well with the observations. The fraction of the predictions within a factor of 2 and 5 of observations exceeds 55% and 82% respectively in the building area and the complex terrain area. This demonstrates the feasibility of the new enhanced modelling for typical Chinese NPP sites.



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eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation

Publication date: Available online 6 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Kyung-Won Min, Sylvia Davila, Richard W. Zealy, Lawson T. Lloyd, In Young Lee, Rumi Lee, Kyung Hye Roh, Ahjin Jung, Jacek Jemielity, Eui-Ju Choi, Jeong Ho Chang, Je-Hyun Yoon
Post-transcriptional gene regulation is an important step in eukaryotic gene expression. The last step to govern production of nascent peptides is during the process of mRNA translation. mRNA translation is controlled by many translation initiation factors that are susceptible to post-translational modifications. Here we report that one of the translation initiation factors, eIF4E, is phosphorylated by Mammalian Ste20-like kinase (MST1). Upon phosphorylation, eIF4E weakly interacts with the 5′ CAP to inhibit mRNA translation. Simultaneously, active polyribosome is more associated with long noncoding RNAs (lncRNAs). Moreover, linc00689-derived a micropeptide, STORM (Stress- and TNF-α-activated ORF Micropeptide), is induced by TNF-α-induced and MST1-mediated eIF4E phosphorylation exhibits molecular mimicry of SRP19 and, thus, competes for 7SL RNA. Our findings have uncovered a novel function of MST1 in mRNA and lncRNA translation by direct phosphorylation of eIF4E. This novel signaling pathway will provide new platforms for mRNA regulation of mRNA translation via post-translational protein modification.



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Gastrointestinal mantle cell lymphoma with isolated mass and multiple lymphomatous polyposis: report of two cases

Abstract

We herein report two patients with mantle cell lymphoma (MCL), who had isolated mass and multiple lymphomatous polyposis (MLP) in the gastrointestinal tract. In case 1, esophagogastroduodenoscopy revealed a protruding mass in the duodenum and double-balloon endoscopy disclosed numerous polypoid lesions in the ileum. Case 2 had polyposis in the duodenum and a large mass-forming lesion in the ascending colon. Based on the histologic and immunohistochemical findings of the biopsy specimens, the diagnosis of MCL was made in both patients. A combination of isolated mass and MLP is considered as characteristic endoscopic findings of intestinal lesions of MCL.

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Interferon-free therapy with sofosbuvir plus ribavirin for successful treatment of genotype 2 hepatitis C virus with lichen planus: a case report

Abstract

Hepatitis C virus (HCV) infection remains the main cause of liver disease and can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV may also develop extrahepatic manifestations in the skin, eyes, joints, kidneys, nervous system, and immune system. In fact, several studies reported that up to 70% of HCV patients experienced extrahepatic manifestations. Lichen planus (LP), which is an immune system disorder that is triggered by viral infections, allergens, and stress, can affect the skin, mouth, nails, and scalp. The association of LP with HCV has been reported, but the effect of HCV treatment on LP remission is controversial. We encountered a 53-year-old man with HCV genotype 2a and LP that were successfully treated with sofosbuvir and ribavirin for 12 weeks. After treatment, he achieved sustained virological response against HCV and remission of erosive LP lesions on the lip. In the era of interferon (IFN)-based treatment for HCV, exacerbation of autoimmune diseases is a common adverse event. Therefore, use of an IFN-free regimen of direct-acting antivirals for HCV might prevent the extrahepatic manifestation of an immune disorder.

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