is implicated in central nervous system, orofacial and maxillofacial anomalies.

Background: Previous studies in mouse, and zebrafish embryos show strong expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 ( in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.

Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies.

Updated Structure of Repeat Expansions in Patients With Myotonic Dystrophy Type 2 and Its Implication for Standard Diagnostics.

Background And Objectives: Myotonic dystrophy type 2 (DM2) is a multisystemic repeat disorder caused by the expansion of an unstable CCTG tetranucleotide repeat in the noncoding region of the gene. Standard diagnostic is based on Southern blot analysis or a unidirectional RP-PCR that amplifies the repeat from the downstream end.

Methods: Our study reevaluated 80 patients (cohort 1) with clinical suspicion of DM2 but homozygous negative results using the standard diagnostic repeat-primed PCR (RP-PCR).

SGLT2-Inhibition in Patients With Alport Syndrome.

Introduction: Large-scale trials showed positive outcomes of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in adults with chronic kidney disease (CKD). Whether the use of SGLT2i is safe and effective in patients with the common hereditary CKD Alport syndrome (AS) has not yet been investigated specifically in larger cohorts.

Methods: This observational, multicenter, international study (NCT02378805) assessed 112 patients with AS after start of SGLT2i.

The Prevention of Maternal Phenylketonuria (PKU) Syndrome: The Development and Evaluation of a Specific Training Program.

Background: Maternal phenylketonuria (PKU) syndrome, leading to severe psychomotor retardation, microcephaly, cardiac defects and undergrowth, affects the unborn children of mothers with PKU with insufficient metabolic control during pregnancy. To improve long-term outcomes, a specific prevention program was developed.

Methods: We designed a group training program for young women with PKU (>14 years) and their partners.

Variants in the AGBL5 gene are responsible for autosomal recessive Retinitis pigmentosa with hearing loss.

The AGBL5 gene encodes for the Cytoplasmic Carboxypeptidase 5 (CCP5), an α-tubulin deglutamylase that cleaves the γ-carboxyl-linked branching point of glutamylated tubulin. To date, pathogenic variants in AGBL5 have been associated only with isolated retinitis pigmentosa (RP). Hearing loss has not been reported in AGBL5-caused retinal disease.

Implementation of the new DGRh S2e guideline on diagnostics and treatment of adult-onset Still's disease in Germany : Implications for clinical practice in rheumatology.

Background: Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease. Since it can lead to variable organ involvement, including life-threatening complications, and due to newly available therapeutic approaches, the German Society for Rheumatology and Clinical Immunology (Deutsche Gesellschaft für Rheumatologie und klinische Immunologie; DGRh) issued a newly developed S2e guideline in December 2022.

Objective: This study aims to investigate the influence of the new guideline on the diagnosis, management, and outcomes of AOSD.

Further delineation of the SCAF4-associated neurodevelopmental disorder.

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.

Concomitant Upd(14)mat and Trisomy 14 Mosaicism in a Newborn Detected by Whole Genome Sequencing.

Maternal uniparental disomy of chromosome 14, upd(14)mat, leads to Temple syndrome (TS), an imprinting disorder characterized by pre- and postnatal growth retardation, hypotonia, motor delay, joint laxity, and precocious puberty. The occurrence of upd(14)mat is rare, and it may, in even rarer cases, co-occur with trisomy 14 mosaicism. To date, only 11 live-born cases have been reported in the literature.

Single-Nucleus RNA Sequencing Reveals the Spatiotemporal Dynamics of Disease-Associated Microglia in Amyotrophic Lateral Sclerosis.

Disease-associated microglia (DAM) are observed in neurodegenerative diseases, demyelinating disorders, and aging. However, the spatiotemporal dynamics and evolutionary trajectory of DAM during the progression of amyotrophic lateral sclerosis (ALS) remain unclear. Using a mouse model of ALS that expresses a human gene mutation, we found that the microglia subtype DAM begins to appear following motor neuron degeneration, primarily in the brain stem and spinal cord.

The eye movement and gait variability analysis in Chinese patients with Huntington's disease.

Background: Huntington's disease disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. But there lacks an integration analysis of eye movement and gait.

Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials.

Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

Biallelic Variants in LRRC45 Impair Ciliogenesis and Cause a Severe Neurological Disorder.

Leucine - rich repeat containing 45 protein (LRRC45) protein localizes at the proximal end of centrioles and forms a component of the proteinaceous linker between them, with an important role in centrosome cohesion. In addition, a pool of it localizes at the distal appendages of the modified parent centriole that forms the primary cilium and it has essential functions in the establishment of the transition zone and axonemal extension during early ciliogenesis. Here, we describe three individuals from two unrelated families with severe central nervous system anomalies.

Severe Disease Activation after Fingolimod Discontinuation in a Pediatric Multiple Sclerosis Patient: A Case Report and Literature Review.

Adult reports of unexpected severe disease worsening, often termed "rebound," shortly after discontinuing fingolimod in a subset of patients with multiple sclerosis (MS), have grown over the last decade. This phenomenon, however, remains poorly described in pediatric MS patients. We present findings of a 15-year-old who experienced a debilitating relapse 4 weeks after stopping fingolimod to switch to ocrelizumab.

ELMO2-related intraosseous vascular malformation: new cases with novel pathogenic variants, clinical follow-up and therapeutic approaches.

Primary intraosseous vascular malformation (VMPI, #606893) is an ultra-rare disorder caused by biallelic pathogenic variants in ELMO2. To date, only six families with pathogenic ELMO2 variants causing a VMPI phenotype have been described. VMPI is characterized by vascular malformations that compress the facial bones, often leading to life-threatening complications, such as massive bleeding and intracranial herniation.

Efficacy of ofatumumab combined with corticosteroids in the treatment of autoimmune encephalitis: a 6-month cohort study.

Objective: This study investigated the efficacy of ofatumumab (OFA) combined with corticosteroids in autoimmune encephalitis (AE) patients refractory to conventional treatment.

Methods: Eighteen AE patients admitted to Ruijin Hospital between June 2022 and September 2023 received four subcutaneous 20-mg OFA injections at 0, 1, 6, and 12 weeks combined with standard corticosteroid therapy.

Results: Clinical symptoms, modified Rankin scale (mRS) scores, Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores, serum immunoglobulin (Ig) levels (IgG and IgM), and peripheral blood CD20 + B cell levels were documented before OFA administration and at 1, 2, 6, 12, and 24 weeks post-treatment.

NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.

N-methyl-D-aspartate receptors (NMDARs) are critical components of the mammalian central nervous system, involved in synaptic transmission, plasticity, and neurodevelopment. This review focuses on the structural and functional characteristics of NMDARs, with a particular emphasis on the GRIN2 subunits (GluN2A-D). The diversity of GRIN2 subunits, driven by alternative splicing and genetic variants, significantly impacts receptor function, synaptic localization, and disease manifestation.

Psychosocial Workloads and Resilience of Heads of Municipal Public Health Authorities in Germany During the COVID-19 Pandemic: Perceptions of Operational Organization, Communication, and Measures.

Healthcare professionals are particularly vulnerable to mental health issues during epidemics, as evidenced by the COVID-19 crisis. German public health authorities, crucial for disease prevention, faced significant strain from chronic understaffing and resource limitations exacerbated by the pandemic. The study was designed as a cross-sectional, observational online survey.

Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives.

The Y chromosome (ChrY) is essential for male sex determination and spermatogenesis. However, recent studies have revealed its broader role in various physiological processes and disease susceptibility, including cancer. A comprehensive literature review was conducted using databases like MEDLINE, Scopus, Web of Science, and Google Scholar.

Thermodynamic versus kinetic basis for the high conformational stability of nanobodies for therapeutic applications.

Nanobodies (NB) are powerful tools for biotechnological and therapeutic applications. They strongly bind to their targets and are very stable. Early studies showed that NB unfolding is reversible and can be analyzed by equilibrium thermodynamics, whereas more recent studies focused on their kinetic stability in very harsh conditions that are far from storage or physiological temperatures (4-37 °C).

GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment.

Here we conduct a study involving 12 individuals with retinal dystrophy, neurological impairment, and skeletal abnormalities, with special focus on GPATCH11, a lesser-known G-patch domain-containing protein, regulator of RNA metabolism. To elucidate its role, we study fibroblasts from unaffected individuals and patients carrying the recurring c.328+1 G > T mutation, which specifically removes the main part of the G-patch domain while preserving the other domains.

Development of a novel tool for individual treatment trials in mucopolysaccharidosis.

Mucopolysaccharidosis (MPS) encompasses a group of genetic lysosomal storage disorders, linked to reduced life expectancy and a significant lack of effective treatment options. Immunomodulatory drugs could have the potential to be a relevant medical approach, as the accumulation of undegraded substances initiates an innate immune response, which leads to inflammation and clinical deterioration. However, immunomodulators are not licensed for this indication.