Germline pathogenic variants in RNF43 in patients with and without serrated polyposis syndrome.

Serrated Polyposis Syndrome (SPS) is characterized by multiple and/or large serrated polyps in the colon and an increased risk of colorectal cancer (CRC). The etiology is largely unknown, but in a subset of patients with SPS, monoallelic pathogenic variants in RNF43 are detected. To date, however, the penetrance and phenotypic spectrum of patients carrying pathogenic variants (PV) in RNF43 are poorly described.

DAHEAN: A Danish nationwide study ensuring quality assurance through real-world data for suspected hereditary anemia patients.

Background: Hereditary anemias are a group of genetic diseases prevalent worldwide and pose a significant health burden on patients and societies. The clinical phenotype of hereditary anemias varies from compensated hemolysis to life-threatening anemia. They can be roughly categorized into three broad categories: hemoglobinopathies, membranopathies, and enzymopathies.

A Rare Case of Beta-Thalassemia Diagnosed by Whole-Genome Sequencing in an Ethnically Danish Newborn.

In 2020, a 2-month-old ethnically Danish girl was diagnosed with β-thalassemia after presenting with persistent jaundice. The peripheral blood smear showed significant aniso- and poikilocytosis, increased number of reticulocytes and erythroblastosis. Trio analysis of the index patient and both parents was performed by whole-genome sequencing.

Glucose phosphate isomerase deficiency demasked by whole-genome sequencing: a case report.

Background: Glucose-6-phosphate isomerase deficiency is a rare genetic disorder causing hereditary nonspherocytic hemolytic anemia. It is the second most common glycolytic enzymopathy in red blood cells. About 90 cases are reported worldwide, with symptoms including chronic hemolytic anemia, jaundice, splenomegaly, gallstones, cholecystitis, and in severe cases, neurological impairments, hydrops fetalis, and neonatal death.

Anomalies of imagination and development of psychosis: A phenomenological account.

In 20th century psychiatry, various disturbances of imagination were discussed in the context of schizophrenia. Today, these notions have almost completely vanished from mainstream psychopathology. However, recent work has suggested that specific phenomena within this area have a relevance for differential diagnosis and early detection of psychosis.

Treatment of schizotypal disorder: a protocol for a systematic review of the evidence and recommendations for clinical practice.

Introduction: Schizotypal disorder is associated with a high level of disability at an individual level and high societal costs. However, clinical recommendations for the treatment of schizotypal disorder are scarce and based on limited evidence. This review aims to synthesise the current evidence on treatment for schizotypal disorder making recommendations for clinical practice.

Quartz-Enhanced Photoacoustic Spectroscopy Assisted by Partial Least-Squares Regression for Multi-Gas Measurements.

We report on the use of quartz-enhanced photoacoustic spectroscopy (QEPAS) for multi-gas detection. Photoacoustic (PA) spectra of mixtures of water (H2O), ammonia (NH3), and methane (CH4) were measured in the mid-infrared (MIR) wavelength range using a mid-infrared (MIR) optical parametric oscillator (OPO) light source. Highly overlapping absorption spectra are a common challenge for gas spectroscopy.

The self, neuroscience and psychosis study: Testing a neurophenomenological model of the onset of psychosis.

Aim: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12-month follow-up.

Methods: SNAP is a longitudinal observational study.

Psychiatric comorbidity: a concept in need of a theory.

Despite being a relatively new concept, psychiatric comorbidity, i.e. the co-occurrence of two or more mental disorders, has become widespread in clinical practice and psychiatric research.

Obsessive-compulsive symptoms in the schizophrenia-spectrum: current developments in psychopathology research.

Purpose Of Review: Schizophrenia-spectrum disorders (SSD) frequently involve symptoms that usually are ascribed to nonpsychotic disorder spectra, such as obsessive-compulsive symptoms (OCS). These symptoms can cause differential diagnostic challenges, particularly in early illness stages, and must be considered in treatment planning. In this review, we provide an overview of recent literature within the field of OCS in SSD, with a focus on psychopathology research.

Pseudoneurotic symptoms in the schizophrenia spectrum: An empirical study.

Background: Nonpsychotic symptoms (depression, anxiety, obsessions etc.) are frequent in schizophrenia-spectrum disorders. Twentieth century foundational psychopathological literature claimed that certain nonpsychotic symptoms (here termed pseudoneurotic symptoms) are relatively closely linked with the schizophrenia-spectrum, despite descriptive overlap with symptoms of other diagnoses.

Are Self-disorders in Schizophrenia Expressive of a Unifying Disturbance of Subjectivity: A Factor Analytic Approach.

Background And Hypothesis: The idea that a disorder of the basic self is a central feature in schizophrenia has recently been corroborated in a meta-analysis and a systematic review. Manifestations of the self-disorder can be systematically explored with the Examination of Anomalous Self-Experience (EASE). In this study, we examined the factorial structure of EASE, and diagnostic efficacy of EASE.

What is obsession? Differentiating obsessive-compulsive disorder and the schizophrenia spectrum.

Obsessive-compulsive symptoms are frequent in schizophrenia-spectrum disorders and often cause differential diagnostic challenges, especially in first-contact patients. Drawing upon phenomenology of cognition, we critically review classic and contemporary psychopathological notions of obsessive-compulsive phenomena and discuss their relevance for differential diagnosis between obsessive-compulsive disorder (OCD) and schizophrenia-spectrum disorders. The classic psychopathological literature defines true obsession as intrusions with intact resistance and insight and regards these features as essential to the diagnosis of OCD.

Anomalies of Imagination, Self-Disorders, and Schizophrenia Spectrum Psychopathology: A Network Analysis.

Background: Anomalies of imagination encompass disturbances of the basic experiential structure of fantasies and imagery that can be explored in a semi-structured way with the Examination of Anomalous Fantasy and Imagination (EAFI). We aimed (1) to examine the distribution of anomalies of imagination among different diagnostic groups and a group of healthy controls, and (2) to examine their relation with disorders of basic self, perceptual disturbances and canonical state psychopathology of the schizophrenia-spectrum (positive, negative and general symptoms).

Methods: The 81 participants included patients with schizophrenia or other non-affective psychosis ( = 32), schizotypal personality disorder ( = 15) or other mental illness ( = 16) and healthy controls ( = 18).

Disordered Selfhood in Schizophrenia and the Examination of Anomalous Self-Experience: Accumulated Evidence and Experience.

Disordered selfhood in schizophrenia was rediscovered at the turn of the millennium. In 2005, Psychopathology published the psychometric instrument, the Examination of Anomalous Self-Experience (EASE). In this article, we summarize the historical background of the creation of the EASE, explicate the notion of the disorder of basic or minimal self with the help of phenomenological philosophy, and provide a brief description of clinical manifestations targeted by the EASE.

The Copenhagen founder variant GP1BA c.58T>G is the most frequent cause of inherited thrombocytopenia in Denmark.

Background: The classic Bernard-Soulier syndrome (BSS) is a rare inherited thrombocytopenia (IT) associated with severe thrombocytopenia, giant platelets, and bleeding tendency caused by homozygous or compound heterozygous variants in GP1BA, GP1BB, or GP9. Monoallelic BSS (mBSS) associated with mild asymptomatic macrothrombocytopenia caused by heterozygous variants in GP1BA or GP1BB may be a frequent cause of mild IT.

Objective: We aimed to examine the frequency of mBSS in a consecutive cohort of patients with IT and to characterize the geno- and phenotype of mBSS probands and their family members.

Substitutional landscape of a split fluorescent protein fragment using high-density peptide microarrays.

Split fluorescent proteins have wide applicability as biosensors for protein-protein interactions, genetically encoded tags for protein detection and localization, as well as fusion partners in super-resolution microscopy. We have here established and validated a novel platform for functional analysis of leave-one-out split fluorescent proteins (LOO-FPs) in high throughput and with rapid turnover. We have screened more than 12,000 variants of the beta-strand split fragment using high-density peptide microarrays for binding and functional complementation in Green Fluorescent Protein.

Chronic migraine: Genetics or environment?

Background: The transition from episodic migraine to chronic migraine, migraine chronification, is usually a gradual process, which involves multiple risk factors. To date, studies of the genetic risk factors for chronic migraine have focused primarily on candidate-gene approaches using healthy individuals as controls.

Aims And Methods: In this study, we used a large cohort of migraine families and unrelated migraine patients (n > 2200) with supporting genotype and whole-genome sequencing data.

Functional gene networks reveal distinct mechanisms segregating in migraine families.

Migraine is the most common neurological disorder worldwide and it has been shown to have complex polygenic origins with a heritability of estimated 40-70%. Both common and rare genetic variants are believed to underlie the pathophysiology of the prevalent types of migraine, migraine with typical aura and migraine without aura. However, only common variants have been identified so far.

Prevalence and socio-demographic characteristics of persons who have never had a headache among healthy voluntary blood donors - a population-based study.

Introduction: Headache is an extremely prevalent disorder with a lifetime prevalence of 90-99%. However, a small fraction of people never experiences a headache. Research on people without headache could uncover protective factors in headache, but to our knowledge no study on headache-free individuals has been published.

Familial analysis reveals rare risk variants for migraine in regulatory regions.

The most recent genome-wide association study of migraine increased the total number of known migraine risk loci to 38. Still, most of the heritability of migraine remains unexplained, and it has been suggested that rare gene dysregulatory variants play an important role in migraine etiology. Addressing the missing heritability of migraine, we aim to fine-map signals from the known migraine risk loci to regulatory mechanisms and associate these to downstream genic targets.

Higher burden of rare frameshift indels in genes related to synaptic transmission separate familial hemiplegic migraine from common types of migraine.

Background: Familial hemiplegic migraine (FHM) is a rare form of migraine with aura that often has an autosomal dominant mode of inheritance. Rare mutations in the , and genes can all cause FHM revealing genetic heterogeneity in the disorder. Furthermore, only a small subset of the affected individuals has a causal mutation.