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.

Medial temporal lobe atrophy relates more strongly to sleep-wake rhythm fragmentation than to age or any other known risk.

Atrophy of the medial temporal lobe of the brain is key to memory function and memory complaints in old age. While age and some morbidities are major risk factors for medial temporal lobe atrophy, individual differences remain, and mechanisms are insufficiently known. The largest combined neuroimaging and whole genome study to date indicates that medial temporal lobe volume is most associated with common polymorphisms in the GRIN2B gene that encodes for the 2B subunit (NR2B) of the NMDA receptor.

Special Issue Introduction: Inherited Retinal Disease: Novel Candidate Genes, Genotype-Phenotype Correlations, and Inheritance Models.

Inherited retinal diseases (IRDs) are genetically and clinically heterogeneous disorders.[..

Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial.

Background: Keeping individuals on antidepressants after remission or recovery of major depressive disorder is a common strategy to prevent relapse or recurrence. Preventive cognitive therapy (PCT) has been proposed as an alternative to maintenance antidepressant treatment, but whether its addition would allow tapering of antidepressants or enhance the efficacy of maintenance antidepressant treatment is unclear. We aimed to compare the effectiveness of antidepressants alone, with PCT while tapering off antidepressants, or PCT added to antidepressants in the prevention of relapse and recurrence.

Psycholinguistic variables matter in odor naming.

People from Western societies generally find it difficult to name odors. In trying to explain this, the olfactory literature has proposed several theories that focus heavily on properties of the odor itself but rarely discuss properties of the label used to describe it. However, recent studies show speakers of languages with dedicated smell lexicons can name odors with relative ease.

Computer face-matching technology using two-dimensional photographs accurately matches the facial gestalt of unrelated individuals with the same syndromic form of intellectual disability.

Background: Massively parallel genetic sequencing allows rapid testing of known intellectual disability (ID) genes. However, the discovery of novel syndromic ID genes requires molecular confirmation in at least a second or a cluster of individuals with an overlapping phenotype or similar facial gestalt. Using computer face-matching technology we report an automated approach to matching the faces of non-identical individuals with the same genetic syndrome within a database of 3681 images [1600 images of one of 10 genetic syndrome subgroups together with 2081 control images].

midigenes reveal the full splice spectrum of all reported noncanonical splice site variants in Stargardt disease.

Stargardt disease is caused by variants in the gene, a significant part of which are noncanonical splice site (NCSS) variants. In case a gene of interest is not expressed in available somatic cells, small genomic fragments carrying potential disease-associated variants are tested for splice abnormalities using in vitro splice assays. We recently discovered that when using small minigenes lacking the proper genomic context, in vitro results do not correlate with splice defects observed in patient cells.

Biomarkers in cerebrospinal fluid for synucleinopathies, tauopathies, and other neurodegenerative disorders.

The incidence of neurodegenerative disorders is increasing due to worldwide population aging. In general, sporadic forms account for 90% of total cases with neurodegenerative disorders and the reasons underlying initiation or progression of these diseases remain unknown for almost all disorders. To date, diagnosis is mainly based on clinical symptoms and neuroimaging, which is in many cases insufficient due to overlap in clinical symptoms among several neurodegenerative disorders.

Recurrent De Novo Mutations Disturbing the GTP/GDP Binding Pocket of RAB11B Cause Intellectual Disability and a Distinctive Brain Phenotype.

The Rab GTPase family comprises ∼70 GTP-binding proteins, functioning in vesicle formation, transport and fusion. They are activated by a conformational change induced by GTP-binding, allowing interactions with downstream effectors. Here, we report five individuals with two recurrent de novo missense mutations in RAB11B; c.

Nonlinear temporal dynamics of cerebral small vessel disease: The RUN DMC study.

Objective: To investigate the temporal dynamics of cerebral small vessel disease (SVD) by 3 consecutive assessments over a period of 9 years, distinguishing progression from regression.

Methods: Changes in SVD markers of 276 participants of the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) cohort were assessed at 3 time points over 9 years. We assessed white matter hyperintensities (WMH) volume by semiautomatic segmentation and rated lacunes and microbleeds manually.

Towards human exploration of space: The THESEUS review series on immunology research priorities.

Dysregulation of the immune system occurs during spaceflight and may represent a crew health risk during exploration missions because astronauts are challenged by many stressors. Therefore, it is crucial to understand the biology of immune modulation under spaceflight conditions in order to be able to maintain immune homeostasis under such challenges. In the framework of the THESEUS project whose aim was to develop an integrated life sciences research roadmap regarding human space exploration, experts working in the field of space immunology, and related disciplines, established a questionnaire sent to scientists around the world.

Defects in the Cell Signaling Mediator β-Catenin Cause the Retinal Vascular Condition FEVR.

Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder characterized by the abnormal development of the retinal vasculature. The majority of mutations identified in FEVR are found within four genes that encode the receptor complex (FZD4, LRP5, and TSPAN12) and ligand (NDP) of a molecular pathway that controls angiogenesis, the Norrin-β-catenin signaling pathway. However, half of all FEVR-affected case subjects do not harbor mutations in these genes, indicating that further mutated genes remain to be identified.

Reduced Freezing in Posttraumatic Stress Disorder Patients while Watching Affective Pictures.

Besides fight and flight responses, animals and humans may respond to threat with freezing, a response characterized by bradycardia and physical immobility. Risk assessment is proposed to be enhanced during freezing to promote optimal decision making. Indeed, healthy participants showed freezing-like responses to threat cues.

Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study.

Purpose: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies.

Design: Retrospective cohort study.

Participants: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families.

Testosterone in human studies: Modest associations between plasma and salivary measurements.

Testosterone is involved in many processes like aggression and mood disorders. As it may easily diffuse from blood into saliva, salivary testosterone is thought to reflect plasma free testosterone level. If so, it would provide a welcome noninvasive and less stressful alternative to blood sampling.

Elimination diets' efficacy and mechanisms in attention deficit hyperactivity disorder and autism spectrum disorder.

Nutrition plays an important role in neurodevelopment. This insight has led to increasing research into the efficacy of nutrition-related interventions for treating neurodevelopmental disorders. This review discusses an elimination diet as a treatment for attention deficit hyperactivity disorder and autism spectrum disorder, with a focus on the efficacy of the food additives exclusion diet, gluten-free/casein-free diet and oligoantigenic diet.

MicroRNAs in Cerebrospinal Fluid as Potential Biomarkers for Parkinson's Disease and Multiple System Atrophy.

Parkinson's disease (PD) and multiple system atrophy (MSA) are both part of the spectrum of neurodegenerative movement disorders and α-synucleinopathies with overlap of symptoms especially at early stages of the disease but with distinct disease progression and responses to dopaminergic treatment. Therefore, having biomarkers that specifically classify patients, which could discriminate PD from MSA, would be very useful. MicroRNAs (miRNAs) regulate protein translation and are observed in biological fluids, including cerebrospinal fluid (CSF), and may therefore have potential as biomarkers of disease.

Tonic immobility differentiates stress responses in PTSD.

Background: Tonic immobility (TI) is a state of physical immobility associated with extreme stress and the development of posttraumatic stress disorder (PTSD). However, it is unknown whether TI is associated with a distinct actual stress response, i.e.

From Perception to Metacognition: Auditory and Olfactory Functions in Early Blind, Late Blind, and Sighted Individuals.

Although evidence is mixed, studies have shown that blind individuals perform better than sighted at specific auditory, tactile, and chemosensory tasks. However, few studies have assessed blind and sighted individuals across different sensory modalities in the same study. We tested early blind ( = 15), late blind ( = 15), and sighted ( = 30) participants with analogous olfactory and auditory tests in absolute threshold, discrimination, identification, episodic recognition, and metacognitive ability.

SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome.

Background: Kohlschütter-Tönz syndrome (KTZS) is a rare autosomal-recessive disease characterised by epileptic encephalopathy, intellectual disability and amelogenesis imperfecta (AI). It is frequently caused by biallelic mutations in ROGDI. Here, we report on individuals with ROGDI-negative KTZS carrying biallelic SLC13A5 mutations.

Perceived Ethnic Discrimination and the Metabolic Syndrome in Ethnic Minority Groups: The Healthy Life in an Urban Setting Study.

Objective: Ethnic differences in the metabolic syndrome could be explained by perceived ethnic discrimination (PED). It is unclear whether PED is associated with the metabolic syndrome. We assessed this association and quantified the contribution of PED to the metabolic syndrome.