Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly identified patients and review of the literature.

De novo germline mutations in GNB1 have been associated with a neurodevelopmental phenotype. To date, 28 patients with variants classified as pathogenic have been reported. We add 18 patients with de novo mutations to this cohort, including a patient with mosaicism for a GNB1 mutation who presented with a milder phenotype.

Alternate gas washout indices: Assessment of ventilation inhomogeneity in mild to moderate pediatric cystic fibrosis lung disease.

Introduction: Normalized phase III slope (Sn ) indices from multiple breath washout (MBW) estimate ventilation inhomogeneity. Alternate (*) protocols for Sn indices exist, however the utility of these outcomes in children with mild-to-moderate cystic fibrosis (CF) is unknown.

Methods: We measured nitrogen MBW and spirometry in 135 children (43 controls) aged 4-18 years.

A novel FBXO28 frameshift mutation in a child with developmental delay, dysmorphic features, and intractable epilepsy: A second gene that may contribute to the 1q41-q42 deletion phenotype.

Chromosome 1q41-q42 deletions have recently been associated with a recognizable neurodevelopmental syndrome of early childhood (OMIM 612530). Within this group, a predominant phenotype of developmental delay (DD), intellectual disability (ID), epilepsy, distinct dysmorphology, and brain anomalies on magnetic resonance imaging/computed tomography has emerged. Previous reports of patients with de novo deletions at 1q41-q42 have led to the identification of an evolving smallest region of overlap which has included several potentially causal genes including DISP1, TP53BP2, and FBXO28.

Prediction of the presence of a seventh ankyrin repeat in IκBε from homology modeling combined with hydrogen-deuterium exchange mass spectrometry (HDX-MS).

The ankyrin repeat (AR) structure is a common protein-protein interaction motif and ankyrin repeat proteins comprise a vast family across a large array of different taxa. Natural AR proteins adopt a conserved fold comprised of several repeats with the N- and C-terminal repeats generally being of more divergent sequences. Obtaining experimental crystal structures for natural ankyrin repeat domains (ARD) can be difficult and often requires complexation with a binding partner.

RNAs interact with BRD4 to promote enhanced chromatin engagement and transcription activation.

The bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters via its bromodomains (BDs) to regulate transcriptional elongation. In human colorectal cancer cells, we found that BRD4 was recruited to enhancers that were co-occupied by mutant p53 and supported the synthesis of enhancer-directed transcripts (eRNAs) in response to chronic immune signaling. BRD4 selectively associated with eRNAs that were produced from BRD4-bound enhancers.

Intranasal immunization with recombinant chlamydial protease-like activity factor attenuates atherosclerotic pathology following Chlamydia pneumoniae infection in mice.

We have shown previously that intranasal vaccination with recombinant chlamydial protease-like activity factor (rCPAF: antigen) and interleukin-12 (IL-12) as an adjuvant induces robust protection against pathological consequences of female genital tract infection with Chlamydia muridarum, a closely related species and a rodent model for the human pathogen Chlamydia trachomatis. Another related species Chlamydia pneumoniae, a human respiratory pathogen, has been associated with exacerbation of atherosclerotic pathology. CPAF is highly conserved among Chlamydia spp.

A novel variant in affects gene expression and is associated with X-linked intellectual disability syndrome.

We investigated the genome of a 5-year-old male who presented with global developmental delay (motor, cognitive, and speech), hypotonia, possibly ataxia, and cerebellar hypoplasia of unknown origin. Whole genome sequencing (WGS) and mRNA sequencing (RNA-seq) were performed on a family having an affected proband, his unaffected parents, and maternal grandfather. To explore the molecular and functional consequences of the variant, we performed cell proliferation assays, quantitative real-time PCR (qRT-PCR) array, immunoblotting, calcium imaging, and neurite outgrowth experiments in SH-SY5Y neuroblastoma cells to compare the properties of the wild-type TATA-box-binding protein factor 1 (), deletion of , and variant p.

Neonatal epileptic encephalopathy caused by de novo GNAO1 mutation misdiagnosed as atypical Rett syndrome: Cautions in interpretation of genomic test results.

Epileptic encephalopathies are childhood brain disorders characterized by a variety of severe epilepsy syndromes that differ by the age of onset and seizure type. Until recently, the cause of many epileptic encephalopathies was unknown. Whole exome or whole genome sequencing has led to the identification of several causal genes in individuals with epileptic encephalopathy, and the list of genes has now expanded greatly.

Comparison of Immediate versus Delayed DIEP Flap Reconstruction in Women Who Require Postmastectomy Radiotherapy.

Background: The authors investigated aesthetic outcome and patient satisfaction in women who have undergone deep inferior epigastric artery perforator (DIEP) flap reconstruction in the setting of postmastectomy radiotherapy. Patients who underwent DIEP flap reconstruction without postmastectomy radiotherapy were the control group.

Methods: Participants who had undergone DIEP flap reconstruction between September 1, 2009, and September 1, 2014, were recruited, answered the BREAST-Q, and underwent three-dimensional surface-imaging.

The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with constitutive variants.

Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous variants. Here we have undertaken a detailed clinical study of 55 individuals with variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations.

Elimination of Mycoplasma contamination in Chlamydia stocks as a result of in vivo passage or plaque isolation.

Objective: This study aims to eliminate Mycoplasma spp. contamination from laboratory stocks of Chlamydia spp. by in vivo passage or by plaque assay.

Randomized Outpatient Trial of Single- and Dual-Hormone Closed-Loop Systems That Adapt to Exercise Using Wearable Sensors.

Objective: Automated insulin delivery is the new standard for type 1 diabetes, but exercise-related hypoglycemia remains a challenge. Our aim was to determine whether a dual-hormone closed-loop system using wearable sensors to detect exercise and adjust dosing to reduce exercise-related hypoglycemia would outperform other forms of closed-loop and open-loop therapy.

Research Design And Methods: Participants underwent four arms in randomized order: dual-hormone, single-hormone, predictive low glucose suspend, and continuation of current care over 4 outpatient days.

Pervasive Targeting of Nascent Transcripts by Hfq.

Hfq is an RNA chaperone and an important post-transcriptional regulator in bacteria. Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq), we show that Hfq associates with hundreds of different regions of the Pseudomonas aeruginosa chromosome. These associations are abolished when transcription is inhibited, indicating that they reflect Hfq binding to transcripts during their synthesis.

The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials.

The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials.

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort.

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort is a prospective birth cohort study investigating the initiating events of cystic fibrosis lung disease during infancy, and their influence on the trajectory of disease progression throughout early childhood. Infants with cystic fibrosis are recruited throughout Switzerland after diagnosis by new-born screening. It is the first European population-based prospective cohort study of infants with cystic fibrosis taking advantage of a nationwide new-born screening programme.

Retinal dysfunction in a presymptomatic patient with Huntington's disease.

Purpose: Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Studies have shown retinal abnormalities in patients and mouse models with HD; however, to our knowledge, no prior research papers evaluated retinal structure and function in a presymptomatic patient with HD. The aim of this report is to present a case of retinal dysfunction in a presymptomatic patient with HD.

De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy.

V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.

The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.

The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted therapeutics. We aimed to compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus systemic/cutaneous lymphocyte antigen (-) "polar" CD4/CD8 and activated T-cell subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood, with appropriate clinical correlations.

The plasmid revisited : new insights into growth kinetics.

Research in chlamydial genetics is challenging because of its obligate intracellular developmental cycle. systems exist that allow studies of different aspects of basic biology of chlamydiae, the murine model is one of great importance and thus an essential research tool. carries a plasmid that has a role in virulence.

A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis.

Developmental and epileptic encephalopathies (DEEs) represent a large clinical and genetic heterogeneous group of neurodevelopmental diseases. The identification of pathogenic genetic variants in DEEs remains crucial for deciphering this complex group and for accurately caring for affected individuals (clinical diagnosis, genetic counseling, impacting medical, precision therapy, clinical trials, etc.).

A day in the life of chromatin: how enhancer-promoter loops shape daily behavior.

Each spring, we get out of bed 1 h ahead of our biological wake-up time due to the misalignment of internal clocks with the light-dark cycle. Genetic discoveries revealed that clock genes encode transcription factors that are expressed throughout many tissues, yet a gap has remained in understanding the temporal dynamics of transcription. Two groups now apply circular chromosome conformation capture and high-throughput sequencing to dissect how "time of day"-dependent changes in chromatin drive core clock oscillations.

Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines.

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined.

Leaks during multiple-breath washout: characterisation and influence on outcomes.

Nitrogen multiple-breath washout (NMBW) is increasingly used in patients with cystic fibrosis. The current European Respiratory Society/American Thoracic Society consensus statement for MBW recommends the rejection of measurements with leaks. However, it is unclear whether this is necessary for all types of leaks.