Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders.

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Prevalence of pathogenic variants of inborn errors of immunity in critically ill children admitted to the pediatric intensive care unit for sepsis: A Moroccan cohort study.

Introduction: Pediatric sepsis remains a leading cause of morbidity and mortality in Africa. Nearly half of pediatric sepsis deaths occur in previously healthy children. The role of inborn errors of immunity (IEI) in susceptibility to sepsis is yet to be identified and their prevalence amongst previously healthy children admitted to the pediatric intensive care unit (PICU) is unclear.

Systems immunology integrates the complex endotypes of recessive dystrophic epidermolysis bullosa.

Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood.

Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease: A Phase II Study.

Background And Objectives: Brain energy deficiency occurs at the early stage of Huntington disease (HD). Triheptanoin, a drug that targets the Krebs cycle, can restore a normal brain energetic profile in patients with HD. In this study, we aimed at assessing its efficacy on clinical and neuroimaging structural measures in HD.

Dent disease: Clinical Practice Recommendations.

Dent disease is a rare X-linked tubulopathy that is characterized by low-molecular-weight (LMW) proteinuria associated with hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and kidney failure between the 3rd and the 5th decades of life in 30-80% of affected males. The disease is most often associated with various manifestations of proximal tubular dysfunction. Affected individuals may present nephrotic range proteinuria which may be misinterpreted and cause diagnostic delay.

Gene therapy for β-thalassemia: current and future options.

Beta-thalassemia is a severe, hereditary blood disorder characterized by anemia, transfusion dependence, reduced life expectancy, and poor quality of life. Allogeneic transplantation of hematopoietic stem cells (HSCs) is the only curative treatment for transfusion-dependent β-thalassemia, but a lack of compatible donors prevents the use of this approach for most patients. Over the past 20 years, the rise of gene therapy and the development of lentiviral vectors and genome-editing tools has extended curative options to a broader range of patients.

Digenic Inheritance Mode in Congenital Hypothyroidism due to Thyroid Dysgenesis: HYPOTYGEN translational cohort study.

Context: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and is chiefly caused by thyroid dysgenesis (CHTD). The inheritance mode of the disease remains complex.

Objectives: Gain insight into the inheritance mode of CHTD.

Vitamin B, B, and B Intakes and Risk of Gastric Cancer: Findings from a Case-Control Study.

Background/objectives: Gastric cancer is one of the leading malignancies worldwide. B vitamins play important roles in DNA synthesis and methylation because they are considered co-enzymes in one-carbon metabolism. There is inconclusive evidence regarding the associations between dietary vitamins B, B, and B with the risk of gastric cancer in different epidemiologic studies.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

Baricitinib Treatment in RNU7-1-Associated Aicardi-Goutières Syndrome in a South African Child: A Case Report.

Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy. Janus kinase (JAK) inhibition has emerged as a potential treatment for AGS. RNU7-1 is one of the most recently discovered genes for AGS, and the clinical effects of JAK inhibition in these patients have not been reported.

Backtracking Cell Phylogenies in the Human Brain with Somatic Mosaic Variants.

Somatic mosaic variants, and especially somatic single nucleotide variants (sSNVs), occur in progenitor cells in the developing human brain frequently enough to provide permanent, unique, and cumulative markers of cell divisions and clones. Here, we describe an experimental workflow to perform lineage studies in the human brain using somatic variants. The workflow consists in two major steps: (1) sSNV calling through whole-genome sequencing (WGS) of bulk (non-single-cell) DNA extracted from human fresh-frozen tissue biopsies, and (2) sSNV validation and cell phylogeny deciphering through single nuclei whole-genome amplification (WGA) followed by targeted sequencing of sSNV loci.

IPNA clinical practice recommendations on care of pediatric patients with pre-existing kidney disease during seasonal outbreak of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic, instigated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly impacted healthcare infrastructures around the globe. While children are usually asymptomatic or have mild symptoms, children with pre-existing kidney conditions require specialized attention. This pivotal report, championed by the International Pediatric Nephrology Association (IPNA), delivers precise and actionable recommendations tailored for pediatric patients with kidney ailments in this pandemic landscape.

Next Generation Phenotyping and Synthetic Faces in Coffin Siris Syndrome.

Diagnostic wandering and delayed management are major issues in rare diseases. Here, we report a new Next-Generation Phenotyping (NGP) model for diagnosing Coffin Siris syndrome (CSS) on clinical photographs among controls and distinguish the different genotypes. This retrospective and prospective study, conducted from 1998 to 2023, included frontal and lateral pictures of confirmed CSS.

Biofeedback rehabilitation in children with encopresis due to retentive constipation using simple tools: a real-world study in a French paediatric centre.

This study aimed to describe the effectiveness of biofeedback (BFB) rehabilitation in children with retentive encopresis (RE). A retrospective, single-institution study was conducted in children with BFB sessions for RE between 2017 and 2020. Manometry data and associated envy scores were analysed.

The Monogenic Landscape of Human Infectious Diseases.

The spectrum of known monogenic inborn errors of immunity is growing, with certain disorder underlying a specific and narrow range of infectious diseases. These disorders reveal the core mechanisms by which these infections occur in various settings, including inherited and acquired immunodeficiencies, thereby delineating the essential mechanisms of protective immunity to the corresponding pathogens. These findings also have medical implications, facilitating diagnosis and improving the management of individuals at risk of disease.

Dietary polyunsaturated fatty acids and gastric cancer.

Polyunsaturated fatty acids (PUFAs) are fatty acids, containing more than one double bond and have both anti-inflammatory properties and inhibit tumor progression effects as well as carcinogenic properties. There is inconclusive evidence regarding the effect of PUFA intake on gastric cancer in diverse populations. We, therefore, aimed to determine the association between PUFA intake and risk of gastric cancer in a hospital-based case-control study comprising 1182 incident cases of gastric cancer and 2965 controls in Vietnam.

Loss-of-function of DDR1 is responsible for a chondrodysplasia with multiple dislocations.

Chondrodysplasias with multiple dislocations are rare skeletal disorders characterized by hyperlaxity, joint dislocations, and growth retardation. Chondrodysplasias with multiple dislocations have been linked to pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis. In this study, by exome sequencing analysis, we identified a homozygous nonsense variant (NM_001297654.

Clinical Practice Recommendations on Kidney Management in Methylmalonic Acidemia: an Expert Consensus Statement From ERKNet and MetabERN.

Methylmalonic acidemias (MMAs) are rare inherited metabolic diseases with multiorgan involvement. Chronic kidney disease (CKD) is a common complication, leading to kidney failure, dialysis, and kidney transplantation (KT). The objective of these guidelines was to develop clinical practice recommendations focusing on specific aspects of the kidney management of this disease.

Active learning for extracting rare adverse events from electronic health records: A study in pediatric cardiology.

Objective: Automate the extraction of adverse events from the text of electronic medical records of patients hospitalized for cardiac catheterization.

Methods: We focused on events related to cardiac catheterization as defined by the NCDR-IMPACT registry. These events were extracted from the Necker Children's Hospital data warehouse.

Overexpression of Egr1 Transcription Regulator Contributes to Schwann Cell Differentiation Defects in Neural Crest-Specific Knockout Mice.

Adenosine deaminase acting on RNA 1 (ADAR1) is the principal enzyme for the adenosine-to-inosine RNA editing that prevents the aberrant activation of cytosolic nucleic acid sensors by endogenous double stranded RNAs and the activation of interferon-stimulated genes. In mice, the conditional neural crest deletion of reduces the survival of melanocytes and alters the differentiation of Schwann cells that fail to myelinate nerve fibers in the peripheral nervous system. These myelination defects are partially rescued upon the concomitant removal of the Mda5 antiviral dsRNA sensor in vitro, suggesting implication of the Mda5/Mavs pathway and downstream effectors in the genesis of mutant phenotypes.

Transcriptome immune-regulatory differences between leprosy patients and type 1 reaction patients, before onset of symptoms.

Leprosy is a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. A major public health and clinical problem are leprosy reactions, which are inflammatory episodes that often contribute to nerve damage and disability. Type I reversal reactions (T1R) can occur after microbiological cure of leprosy and affect up to 50% of leprosy patients.