Attenuation of visual exploration following stress.

When we explore our surroundings, we frequently move our gaze to collect visual information. Studies have extensively examined gaze behavior in response to different visual scenes. Here, we examined how differences in an individual's state may affect visual exploration, for example, following acute stress.

A pathogenic CTBP1 variant featuring HADDTS with dystrophic myopathology.

HADDTS (Hypotonia, Ataxia, Developmental-Delay and Tooth-enamel defects) is a newly emerging syndrome caused by CTBP1 mutations. Only five reports (13 cases) are available; three contained muscle-biopsy results but none presented illustrated histomyopathology. We report a patient in whom whole-exome sequencing revealed a heterozygous de novo CTBP1 missense mutation (c.

Clinical and biological profile of Sickle Cell Anemia children in a rural area in Central Africa.

Background: Sickle Cell Anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene . The disease severity is very variable and depends on many factors. We evaluated the clinical and biological profile of sickle cell anemia children in rural Central Africa.

IPSC reprogramming of two patients with spondyloepiphyseal dysplasia congenita (SEDC).

Spondyloepiphyseal dysplasia congenita (SEDC) is a severe non-lethal type 2 collagenopathy caused by pathogenic variants in the COL2A1 gene, which encodes the alpha-1 chain of type II collagen. SEDC is clinically characterized by severe short stature, degenerative joint disease, hearing impairment, orofacial anomalies and ocular manifestations. To study and therapeutically target the underlying disease mechanisms, human iPSC-chondrocytes are considered highly suitable as they have been shown to exhibit several key features of skeletal dysplasias.

IPSC reprogramming of two patients with spondyloepimetaphyseal dysplasia (SEMD, biglycan type).

Hemizygous missense variants in the X-linked BGN gene, encoding the extracellular matrix protein biglycan, cause spondyloepimetaphyseal dysplasia (SEMD, biglycan type), which is clinically characterized by short stature, brachydactyly and osteoarthritis. Little is known about the pathomechanisms underlying SEMD, biglycan type. IPSC-derived chondrocyte disease models have been shown to exhibit several key aspects of known disease mechanisms of skeletal dysplasias and are therefore considered highly suitable human disease models to study SEMD, biglycan type.

Co-Occurrence of Hypohidrotic Ectodermal Dysplasia and Food Protein-Induced Enterocolitis Syndrome: A Report of a New Ectodysplasin A Variant.

Introduction: Ectodermal dysplasias (EDs) are a large group of rare and complex genetic disorders, affecting the development of two or more ectodermal structures. Hypohidrotic ED (HED) is the most frequent ED's phenotype and is characterized by hypodontia, hypotrichosis, and hypo/anhidrosis, leading to heat intolerance and hyperthermia.

Case Presentation: We report a case of a 2-year-old girl with hair and teeth abnormalities associated with severe digestive symptoms responsible for failure to thrive.

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.

Identification of differentially methylated regions in rare diseases from a single-patient perspective.

Background: DNA methylation (5-mC) is being widely recognized as an alternative in the detection of sequence variants in the diagnosis of some rare neurodevelopmental and imprinting disorders. Identification of alterations in DNA methylation plays an important role in the diagnosis and understanding of the etiology of those disorders. Canonical pipelines for the detection of differentially methylated regions (DMRs) usually rely on inter-group (e.

Clinical and laboratory characterization of adult sickle cell anemia patients in Kinshasa.

Background: Sickle cell anemia (SCA) is a monogenic hemoglobinopathy associated with severe acute and chronic complications, with the highest incidence worldwide in Sub-Saharan Africa. The wide variability in clinical manifestations suggest that a uniform response to hydroxurea may not be attained. In view of a potential treatment with hydroxyurea (HU), we assessed the variability of clinical and hematological manifestations in a cohort of adults with SCA in Kinshasa, capital of the DR Congo in Central Africa.

Clinical and molecular diagnosis of genodermatoses: Review and perspectives.

Genodermatoses are a complex and heterogeneous group of genetic skin disorders characterized by variable expression and clinical and genetic heterogeneity, rendering their diagnosis challenging. DNA-based techniques, like whole-exome sequencing, can establish a diagnosis in 50% of cases. RNA-sequencing is emerging as an attractive tool that can obtain information regarding gene expression while integrating functional genomic data with regard to the interpretation of variants.

Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes.

Background: Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype-phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing.

An Appraisal to Address Health Consequences of Vitamin D Deficiency With Food Fortification and Supplements: Time to Act!

A symposium entitled "Vitamin D in Prevention and Therapy" was held on May 4-5, 2022, in Homburg, Germany to discuss important new advances in the field, including identification of new vitamin D signaling pathways, of new biologic effects of vitamin D-compounds (e.g., on the microbiome), and convincing proof of the relevance of vitamin D deficiency for the risk and outcome of many chronic diseases, including cancer, cardio-vascular, auto-immune, metabolic, and infectious diseases.

Comparative study of keratinocyte primary culture methods from paediatric skin biopsies for RNA-sequencing.

Background: Keratinocyte culture is a standard method used to study gene expression, cell differentiation and proliferation. Numerous protocols exist, however their application is frequently unsuitable for small specimens, such as 4-mm punch skin biopsies.

Aims: This study compared 3 different methods of keratinocyte culture from paediatric skin biopsies to evaluate which one ensures adequate cell growth for RNA extraction and sequencing.

Value of DNA testing in the diagnosis of sickle-cell anemia in childhood in an environment with a high prevalence of other causes of anemia.

Background: Sickle-cell anemia (SCA) is the most common genetic disease worldwide caused by a single mutation in the gene HBB. DNA testing can help to clarify the diagnosis when Hb electrophoresis is inconclusive. We evaluated the usefulness and feasibility of DNA-based diagnosis of SCA in rural Central Africa.

Cancer risk and tumour spectrum in 172 patients with a germline pathogenic variation: a collaborative study of the SIOPE Host Genome Working Group.

Background: Little is known about risks associated with germline pathogenic variants (PVs) known as a cancer predisposition syndrome.

Methods: To study tumour risks, we have analysed data of a large cohort of 45 unpublished patients with a germline PV completed with 127 previously published patients. To reduce the ascertainment bias due to index patient selection, the risk of tumours was evaluated in relatives with PV (89 patients) using the Nelson-Aalen estimator.

Social evaluation under stress: Does acute stress affect social attributions and eye gaze?

Acute stress has been found to elicit pro-social, anti-social or null responses in humans. The causes for these contradicting findings are currently poorly understood, and may rise from subjects' characteristics, such as sex or hormonal status, as well as stimuli-based traits, such as group membership. In the current study, 120 subjects performed either the Trier Social Stress Test or a control (non-stress inducing) condition, followed by ranking displayed faces according to several attributes (e.

Carbamazepine efficacy in a severe electro-clinical presentation of SLC13A5-epilepsy.

Recessive mutations in the SLC13A5 gene encoding the sodium-dependent citrate transporter are a recently identified cause of developmental and epileptic encephalopathy. Here, we describe a child harboring a novel homozygous loss-of-function mutation in the SLC13A5 gene (c.1496C>T-p.

Empathy Modulates the Effect of Stress Reactivity on Generous Giving.

How does acute stress influence the degree to which we cooperate with others? Research on the effects of stress on social decision-making is guided by two seemingly contrasting theories. Acute stress may trigger a Fight-or-Flight response, manifested by increased anxiety, and more egocentric or selfish behavior. Alternatively, according to the Tend-and-Befriend model, acute stress may induce affiliative behaviors, marked by increased prosociality in an effort to seek and receive social support and protection.

Scaling up oligogenic diseases research with OLIDA: the Oligogenic Diseases Database.

Unlabelled: Improving the understanding of the oligogenic nature of diseases requires access to high-quality, well-curated Findable, Accessible, Interoperable, Reusable (FAIR) data. Although first steps were taken with the development of the Digenic Diseases Database, leading to novel computational advancements to assist the field, these were also linked with a number of limitations, for instance, the ad hoc curation protocol and the inclusion of only digenic cases. The OLIgogenic diseases DAtabase (OLIDA) presents a novel, transparent and rigorous curation protocol, introducing a confidence scoring mechanism for the published oligogenic literature.

A review of normative documents on preimplantation genetic testing: Recommendations for PGT-P.

Purpose: Recently, preimplantation genetic testing (PGT) for polygenic conditions (PGT-P) has been introduced commercially. In view of the lack of specific guidance on this development, we analyzed normative documents on PGT for monogenic conditions (PGT-M) to understand what we can learn from these documents for recommendations for PGT-P.

Methods: We conducted a systematic review of normative guidelines and recommendations on PGT-M.

Evaluation of neurodevelopmental symptoms in 10 cases of neonatal ichthyosis and sclerosing cholangitis syndrome.

Neonatal ichthyosis and sclerosing cholangitis (NISCH) syndrome is an extremely rare entity with only 19 patients described in the literature. We report an extended family with the disorder and investigate the association of neurodevelopmental symptoms. Patients with CLDN1 mutations, and specifically « the Moroccan» c.

Monitoring of Leukemia Clones in B-cell Acute Lymphoblastic Leukemia at Diagnosis and During Treatment by Single-cell DNA Amplicon Sequencing.

Acute lymphoblastic leukemia (ALL) is characterized by the presence of chromosomal changes, including numerical changes, translocations, and deletions, which are often associated with additional single-nucleotide mutations. In this study, we used single cell-targeted DNA sequencing to evaluate the clonal heterogeneity of B-ALL at diagnosis and during chemotherapy treatment. We designed a custom DNA amplicon library targeting mutational hotspot regions (in 110 genes) present in ALL, and we measured the presence of mutations and small insertions/deletions (indels) in bone marrow or blood samples from 12 B-ALL patients, with a median of 7973 cells per sample.