Long-Term Clinical Characterization of ENTPD1-Related Spastic Paraplegia: A Novel Variant and Comprehensive Literature Review.

Hereditary spastic paraplegia (HSP) represents a genetically heterogeneous group of neurodegenerative disorders characterized by progressive axonal degeneration of corticospinal upper motor neurons, leading to lower limb-predominant spasticity and weakness. To date, 83 HSP subtypes have been reported, exhibiting either pure or complicated phenotypes. Among these, spastic paraplegia type 64 (SPG64) is an ultra-rare form of complicated HSP caused by biallelic variants in ENTPD1, which encodes an ectonucleotidase involved in purine metabolism.

Global dynamics behind enzyme catalysis, evolution, and design.

Enzymes are inherently dynamic entities, with their functions intricately governed by the interplay between conformational dynamics - ranging from local residue fluctuations to global motions - and biochemical activity. Deciphering how such dynamics coordinate higher-order cooperativity across multiple timescales to drive catalysis remains a fundamental challenge. This mini-review highlights the role of large-scale, collective motions involving domain-level displacements and hinge-based rearrangements, which not only facilitate substrate recognition, transformation, and release, but also emerge from and propagate through multidirectional allosteric interactions.

Drought-Induced genomic and epigenetic variations in Quinoa genotypes revealed by iPBS and CRED-iPBS marker systems.

Drought stress significantly impacts crop productivity, yet its influence on genomic and epigenetic variation in quinoa remains poorly understood. This study aimed to assess DNA damage and cytosine methylation alterations in six quinoa genotypes (Titicaca, Rainbow, Moqu Arrochilla, Cherry Vanilla, China, and White) exposed to five irrigation levels (5%, 10%, 25%, 50%, and 100% field capacity). Genomic changes were evaluated using inter-primer binding site (iPBS) markers, while DNA methylation was analyzed via CRED-iPBS.

Reevaluatıng Pı-rads 3 Lesıons Upgraded to 4: The Emergence of a New Subgroup?

Objectives: The study aims to evaluate PI-RADS 4 lesions, including those with primary diffusion restriction (diffusion-weighted imaging score 4) and those upgraded from PI-RADS 3 due to positive dynamic contrast-enhanced findings, and to compare outcomes between these groups while also assessing cancer detection rates and prostatitis between upgraded cases and PI-RADS 3 lesions.

Methods: In this single-center cohort study, peripheral zone lesions classified as PI-RADS 3 and 4 by multiparametric magnetic resonance imaging (MRI) and biopsied via MRI/Transrectal ultrasound-guided targeted biopsy were analyzed.

Results: Of 420 peripheral zone lesions from 272 patients, 202 were PI-RADS 3, 81 PI-RADS 3 + 1, and 137 PI-RADS 4.

Ketamine's impact on mood after day-case surgery and its relation to obesity: a randomised controlled trial in women undergoing fractional curettage.

Background: Several studies have shown that ketamine has an effect on mood and depression in the perioperative context; however, little is known about ketamine's effect on patients' emotional recovery after day-case surgery. We aimed to examine whether a single subanaesthetic dose of ketamine could improve acute mood in patients shortly following fractional curettage.

Methods: One hundred forty women from 202 consecutive fractional curettage patients were enrolled in this randomised, double-blind placebo-controlled single-centre trial.

Developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep: A single tertiary center experience.

Objectives: This study aimed to analyze the clinical characteristics, etiology, neuroimaging, treatment, neurocognitive and EEG outcomes of patients with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (D/EE-SWAS).

Methods: Patients diagnosed with D/EE-SWAS, between 2014 and 2021, with a spike-wave index (SWI) ≥50 % in NREM sleep EEG, were analyzed retrospectively. Outcome measures included neurocognitive assessment, SWI, and seizure frequency.

Insights into therapeutic discovery through the Kelch domain structure of Keap1 at ambient temperature.

Background/aim: The Kelch-like-ECH associated protein 1 (Keap1) is an integral component of the E3-ubiquitin ligase complex, which binds to Nuclear factor erythroid 2-related factor 2 (Nrf2) and facilitates its degradation by the 26S proteasome. The Kelch domain of Keap1, composed of six repeated structural motifs, plays a key role in this interaction. This study aims to investigate the dimeric structure of the Keap1 Kelch domain at ambient temperature and to examine its implications for conformational dynamics, particularly in relation to the DMF and Nrf2 binding sites.

Imaging of renal pseudotumors in children: a comprehensive review.

Certain renal developmental anomalies and non-tumorous lesions in children may mimic malignant tumors, leading to diagnostic challenges. These lesions, known as pseudotumors, require careful differentiation to avoid unnecessary invasive procedures. In this context, imaging techniques play a critical role in differentiating pseudotumors from malignant neoplasms.

Deciphering Allosteric Disease Mutations Through Intrinsic Dynamics.

Allosteric regulation, driven by conformational and dynamic changes, is fundamental to many biological processes. A major challenge in disease genomics is understanding how specific somatic missense mutations affect protein function, especially when their impact structurally and functionally indirect. In this study, we investigate the link between such mutations and intrinsic protein dynamics, focusing on their allosteric roles.

The evolving genetic landscape of neuromuscular fetal akinesias.

Fetal akinesia is a broad term used to describe absent (or reduced, fetal hypokinesia) fetal movements, and it can be detected as early as the first trimester. Depending on the developmental age of onset, anything that interferes or limits the normal movement results in a range of deformations affecting multiple organs and organ systems. Arthrogryposis, also termed arthrogryposis multiplex congenita (AMC), is a definitive terminology for multiple congenital contractures, with two major subgroups; amyoplasia and distal arthrogryposis (DA).

Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases.

Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is not always specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants. Here, we analyzed a cohort of 6,660 rare disease families (5,625 genetically undiagnosed [84%]) from the Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) Consortium, as well as other rare disease cohorts.

Characterization of severe COL6-related dystrophy due to the recurrent variant COL6A1 c.930+189C>T.

Collagen VI-related dystrophies manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with prominent congenital symptoms and characterized by progressive muscle weakness, joint contractures and respiratory insufficiency, to Bethlem muscular dystrophy, with milder symptoms typically recognized later and at times resembling a limb girdle muscular dystrophy, and intermediate phenotypes falling between UCMD and Bethlem muscular dystrophy. Despite clinical and muscle pathology features highly suggestive of collagen VI-related dystrophy, some patients had remained without an identified causative variant in COL6A1, COL6A2 or COL6A3. With combined muscle RNA sequencing and whole-genome sequencing, we uncovered a recurrent, de novo deep intronic variant in intron 11 of COL6A1 (c.

Multidisciplinary Tumor Board Evaluation of Pediatric Patients with Adrenocortical Tumors Across Seven International Centers.

Background: The management of rare tumors at reference centers with specialized multidisciplinary tumor boards (MTBs) improves patient survival. No international standardized diagnostic and treatment recommendations for pediatric patients with adrenocortical carcinoma (ACC) exist so far. The aim of this case-based study is to determine how congruent treatment recommendations are in different specialized institutions in different countries.

SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis.

As a major component of intracellular trafficking, the coat protein complex II (COPII) is indispensable for cellular function during embryonic development and throughout life. The 4 SEC24 proteins (A-D) are essential COPII components involved in cargo selection and packaging. A human disorder corresponding to alterations of SEC24 function is currently known only for SEC24D.

Etiologic spectrum and neurological outcomes in pediatric arterial ischemic stroke and cerebral sinovenous thrombosis: A 15-Year retrospective study at a tertiary hospital.

Objectives: To evaluate clinical and radiological features, risk factors, etiology, treatment approaches, and outcomes of pediatric arterial ischemic stroke (AIS) and cerebral sinovenous thrombosis (CSVT).

Methods: Children beyond the neonatal period diagnosed with AIS or CSVT between 2002 and 2017 were retrospectively analyzed. Demographics, clinical presentations, radiological findings, risk factors, etiologies, treatments, and outcomes were reviewed.

Prenatal predictors of ventriculoperitoneal shunt requirement and adverse perinatal outcomes in newborns with open spina bifida.

Objective: Spina bifida is a group of anomalies that, while non-lethal, require careful prenatal evaluation and prognosis prediction due to their association with common motor and cognitive problems. In this study, we investigated the need for postnatal ventriculoperitoneal shunting (VPS) in fetuses with open spina bifida and explored the relationship between adverse perinatal outcomes and prenatal ultrasonographic findings.

Methods: In this retrospective study, fetuses with open spina bifida that were diagnosed prenatally and resulted in a live birth were examined.

Comparison of Shear Wave Elastography Measurements in Chronic Kidney Disease Patients and Healthy Volunteers.

To evaluate renal parenchymal stiffness using 2D shear wave elastography (SWE) in patients with chronic kidney disease (CKD) and to investigate the correlation between SWE results and demographic as well as laboratory findings. We evaluated 41 CKD patients and 40 controls who underwent abdominal ultrasound (US) between December 2020 and November 2022. SWE measurements were performed by a single radiologist, assessing renal stiffness in the lower pole, middle section, and upper pole of each kidney.

Distinct whole-body muscle MRI imaging patterns in PAX7-congenital myopathy: A case report.

PAX7 is a myogenesis transcription factor important for satellite cell specification and function and thus involved in muscle growth, maintenance, repair and regeneration. Recently, a new autosomal recessive congenital myopathy was described that is caused by biallelic variants in . Our aim is to describe phenotype and whole-body muscle MRI with follow-up imaging findings in a patient with a novel homozygous missense variant in We also compare our patients' imaging features with a patient reported in the initial study, to identify a possible emerging pattern for PAX7-congenital myopathy.

Radiological and clinical signatures to differentiate hepatocellular carcinoma from hepatoblastoma in children older than 5 years of age: a feasibility study.

Background: Hepatoblastoma and hepatocellular carcinoma (HCC) are the most common primary malignant liver tumors in children. Although some characteristic imaging findings have been described in both hepatoblastoma and HCC, it is difficult to distinguish between these two tumors over the 5 years of age.

Objective: To investigate clinical and radiological findings that may help differentiate hepatoblastoma and HCC over 5 years of age.

Neurogenic arthrogryposis, hypotonia, dysmorphic features plus malformation of cortical development further expands the ARL6IP1 loss-of-function phenotype.

Biallelic variants in ARL6IP1 are associated with a rare, complicated form of progressive hereditary spastic paraplegia. Among the few cases reported thus far, two distinct phenotypic clusters with upper and lower motor neuron pathology and varying severities have emerged. Here, we describe a proband who presented with decreased fetal movements, intrauterine growth retardation, arthrogryposis multiplex congenita (AMC), dysmorphic features, weakness and hypotonia.

Real-life experience on efficacy and safety of setmelanotide treatment in prepubertal children.

Monogenic obesity, characterized by severe, early-onset obesity due to single-gene defects, often resists traditional weight management strategies. This report presents real-life experiences on the efficacy and safety of setmelanotide, an MC4R agonist, in 4 prepubertal children (ages 3-9) with LEPR and POMC deficiencies. Findings indicate that setmelanotide is effective at lower doses in our patients with POMC deficiency (0.

Computational and experimental mapping of the allosteric network of two manganese ABC transporters.

Transition metals (e.g., Fe, Zn, Mn) are essential enzymatic cofactors in all organisms.