Brain malformations and seizures by impaired chaperonin function of TRiC.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures.

Unveiling women's lived experiences with care provided by a pregnancy heart team: A qualitative phenomenological study.

Objective: The purpose of this study was to gain an in-depth understanding of the lived experiences of women with CVD regarding their care by a pregnancy heart team (PHT) during pregnancy and the immediate postpartum period.

Methods: Using a qualitative phenomenological study, data were collected through semi-structured interviews with 13 women receiving follow-up care from a PHT at a large tertiary center. Data were collected between December 2022 and September 2023, and thematic content analysis was conducted.

The Genetic Puzzle of Cerebral Palsy: Results of a Monocentric Study.

Background: Cerebral palsy (CP) is the most frequent cause of motor impairment in children. Although perinatal asphyxia was long considered to be the leading cause of CP, recent studies demonstrate its causation in only around one in 10 individuals with CP. Instead, genetic causes are increasingly demonstrated.

Unlocking Japan's cervical cancer prevention deadlock.

Cervical cancer prevention in Japan, which had nearly halted due to misinformation, is now recovering through HPV vaccination and screening efforts. While significant progress has been made, much work remains, yet the recent improvements are highly encouraging.

Sotos Syndrome: Deep Neuroimaging Phenotyping Reveals a High Prevalence of Malformations of Cortical Development.

Background And Purpose: Sotos syndrome is a rare autosomal dominant condition caused by pathogenic mutations in the gene that presents with craniofacial dysmorphism, overgrowth, seizures, and neurodevelopmental delay. Macrocephaly, ventriculomegaly, and corpus callosal dysmorphism are typical neuroimaging features that have been described in the medical literature. The purpose of this study was to expand on the neuroimaging phenotype by detailed analysis of a large cohort of patients with genetically proved Sotos syndrome.

Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.

The shift to a genotype-first approach in genetic diagnostics has revolutionized our understanding of neurodevelopmental disorders, expanding both their molecular and phenotypic spectra. Kleefstra syndrome (KLEFS1) is caused by EHMT1 haploinsufficiency and exhibits broad clinical manifestations. EHMT1 encodes euchromatic histone methyltransferase-1-a pivotal component of the epigenetic machinery.

Arterial aneurysm and dissection: toward the evolving phenotype of Tatton-Brown-Rahman syndrome.

Background: Tatton-Brown-Rahman syndrome (TBRS) is a rare disorder, caused by heterozygous pathogenic variants, and first described in 2014. TBRS is characterised by overgrowth, intellectual disability, facial dysmorphism, hypotonia and musculoskeletal features, as well as neurological and psychiatric features. Cardiac manifestations have also been reported, mainly congenital malformations such as atrial septal defect, ventricular septal defect and cardiac valvular disease.

Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals.

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5].

Explanatory variables of objectively measured 24-h movement behaviors in people with prediabetes and type 2 diabetes: A systematic review.

Aim: Physical activity (PA), sedentary behavior (SB) and sleep (i.e. 24-h movement behaviors) are associated with health indicators in people with prediabetes and type 2 diabetes (T2D).

Novel presentation of AADC deficiency as a mild phenotype with exercise-induced dystonic crises: A case report.

Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive neurometabolic disorder caused by biallelic pathogenic variants in the gene; approximately 140 patients have been described worldwide. AADC deficiency is characterised by a combined deficiency of dopamine, serotonin, adrenaline and noradrenaline causing a highly variable phenotype with developmental delay, early-onset hypotonia, movement disorders and autonomic symptoms. We expand the phenotype of this neurometabolic disorder by reporting on a paediatric patient with a mild phenotype with atypical exercise-induced dystonic crises, a feature that has not been described in AADC deficiency up till now.

Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives.

Toward reporting standards for the pathogenicity of variant combinations involved in multilocus/oligogenic diseases.

Although standards and guidelines for the interpretation of variants identified in genes that cause Mendelian disorders have been developed, this is not the case for more complex genetic models including variant combinations in multiple genes. During a large curation process conducted on 318 research articles presenting oligogenic variant combinations, we encountered several recurring issues concerning their proper reporting and pathogenicity assessment. These mainly concern the absence of strong evidence that refutes a monogenic model and the lack of a proper genetic and functional assessment of the joint effect of the involved variants.

Phenotype of COL3A1/COL5A2 deletion patients.

Introduction: The diagnosis of Ehlers-Danlos syndrome is usually based on well-defined diagnostic criteria and the result of DNA investigation. Classical (cEDS) and vascular type (vEDS) are the most prevalent subtypes and are caused by heterozygous pathogenic variants in COL5A1, COL5A2, COL1A1 or, respectively, in COL3A1. We describe 3 cases with contiguous deletions resulting in haploinsufficiency of both genes with relative mild features of connective tissue disease.

Flow-controlled ventilation in moderate acute respiratory distress syndrome due to COVID-19: an open-label repeated-measures controlled trial.

Background: Flow-controlled ventilation (FCV), a novel mode of mechanical ventilation characterised by constant flow during active expiration, may result in more efficient alveolar gas exchange, better lung recruitment and might be useful in limiting ventilator-induced lung injury. However, data regarding FCV in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome (ARDS) are scarce.

Objectives: We hypothesised that the use of FCV is feasible and would improve oxygenation in moderate COVID-19 ARDS compared to conventional ventilation.

Interpretation and actionability of genetic variants in cardiomyopathies: a position statement from the European Society of Cardiology Council on cardiovascular genomics.

This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family.

Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease.

Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood.

Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features.

Meester-Loeys Syndrome.

Meester-Loeys syndrome is an X-linked form of syndromic thoracic aortic aneurysm, characterized by the involvement of multiple organ systems. More specifically, the cardiovascular, skeletal, craniofacial, cutaneous and neurological systems are affected. Clear clinical overlap with Marfan syndrome and Loeys-Dietz syndrome is observed.