Journals
2026 EN
Kim Gabriela Jeesoo · Malaquias Alexsandra Christianne · Bertola Debora Romeo
+7 more
ABSTRACT Noonan Syndrome (NS) is a clinically and genetically heterogeneous condition characterized by typical facial dysmorphisms, short stature, congenital heart defects, and developmental delays. While variants in genes such as PTPN11 , SOS1 , and RAF1 account for most genetically confirmed cases, diagnosis is challenging due to phenotypic overlap with other syndromes. In this retrospective study, we reviewed 192 patients with a clinical diagnosis of NS at a single tertiary center. Genetic diagnosis of NS was confirmed in 133 patients (69.4%) and diagnosis of non‐NS RASopathies was confirmed in 5 patients via targeted RASopathy panels. Exome sequencing (ES) was performed in 20 of the undiagnosed patients. In six cases, alternative genetic diagnoses were established due to variants in SETD5 , BRPF1 , DPH1 , ACTB , CREBBP , and GATA4 , genes associated with syndromes presenting overlapping phenotypes with NS. Our findings emphasize the utility of a hypothesis‐free approach that uses phenotypic features to prioritize variants in resolving diagnostic uncertainty in NS‐like presentations. These findings also highlight the need to broaden differential diagnoses beyond RASopathies when genetic confirmation of NS cannot be established.
Journals
2026 EN
Giuntini Martina · Picchi Lucia · Cafforio Gianfranco
+4 more
ABSTRACT We present the case of a 61‐year‐old woman with late‐onset hyperkinetic movement disorder, characterized by involuntary, choreiform movements predominantly affecting the right limbs. Symptoms began at age 60 and were exacerbated by emotional stress. Neurological and neurocognitive evaluations were unremarkable, and extensive diagnostic workup, including Magnetic Resonance Imaging (MRI), Electroencephalogram (EEG), Positron Emission Tomography with Fluorodeoxyglucose (FDG‐PET) and genetic testing for common movement disorders, was largely negative. Notably, a heterozygous pathogenic variant (c.736C>T; p.Arg246Trp) in the GLRA1 gene was identified via exome sequencing. This gene encodes a glycine receptor subunit associated with Hyperekplexia (HPX), a rare neurometabolic disorder typically presenting in infancy with exaggerated startle responses. Although our patient did not show a classic HPX phenotype, the clinical picture included emotionally triggered motor symptoms and a positive response to clonazepam, a hallmark of HPX treatment. Clonazepam monotherapy at low doses led to sustained symptom control, while other treatments were less effective. Family history revealed similar late‐onset symptoms in the patient's father, though undocumented. This case expands the phenotypic spectrum of HPX and suggests that atypical presentations may be misclassified as functional neurological disorders. It underscores the importance of genetic evaluation in unexplained adult‐onset movement disorders and raises the possibility of underrecognized late‐onset HPX variants in clinical practice.
Journals
2026 EN
De Falco Alessandro · Vincent Marie · Vieville Gaëlle
+33 more
ABSTRACT Copy number variants (CNV) are a major cause of neurodevelopmental disorders. Novel CNV syndromes may still be unrecognized. We report a 9q34.11 microduplication syndrome characterized by neurodevelopmental impairment and recurrent facial anomalies. Following the identification of a de novo 9q34.11 microduplication involving the SET and SPTAN1 genes in an 11‐year‐old girl with speech delay, intellectual disability, and behavioral abnormalities, we identified 13 additional patients with overlapping duplications. Besides the neurodevelopmental disorder, clinical features observed among affected individuals included recurrent dysmorphic features, such as midface hypoplasia and thin lips. The minimal region of overlap among these cases contained the SET gene, suggesting that its triplosensitivity may play a role in the observed phenotypes.
Journals
2026 EN
Al Shamsi Bushra · Al Maimani Ashwaq · Al Hanaie Maria
+3 more
ABSTRACT Autosomal recessive spinocerebellar ataxia type 20 (SCAR20) is a rare neurodevelopmental disorder caused by biallelic variants in the SNX14 gene and characterized by developmental delay, hypotonia, cerebellar atrophy, and hearing loss. This study aimed to characterize the clinical, radiological, and genetic presentation of affected individuals in a consanguineous Omani population. We conducted a retrospective and partly prospective case series involving 17 patients from seven consanguineous families seen at the Royal Hospital, Oman. Data were collected between September and November 2024, with historical assessments extending over the past decade. Clinical data were extracted from electronic records, and neuroimaging was reviewed. Whole exome sequencing of seven probands was performed, and familial segregation was confirmed through targeted Sanger sequencing. Variants were classified according to American College of Medical Genetics and Genomics (ACMG) guidelines. The most common variant was SNX14 c.647_648del (p.Glu216Valfs24), identified in seven patients. Four patients carried the c.1132C>T (p.Arg378) variant, while two had a novel splice‐site mutation, c.613‐1G>A. One case involved a contiguous gene deletion affecting NT5E. Patient ages ranged from 1 month to 21 years. This report expands the mutational and clinical spectrum of SCAR20 in the Middle East and highlights the importance of early genetic testing, diagnostic vigilance, and multidisciplinary care in consanguineous populations.
Journals
2026 EN
Colona Vito Luigi · Gnazzo Maria · Genovese Silvia
+13 more
ABSTRACT We describe a novel homozygous intragenic deletion in the ALS2 gene in an 8‐year‐old boy with Infantile‐onset Ascending Hereditary Spastic Paraplegia (IAHSP) and oculomotor apraxia, thereby contributing to the expanding genetic landscape of ALS2 ‐related disorders. Comprehensive neurological evaluation, chromosomal microarray analysis (CMA), and trio‐based whole exome sequencing (WES) were performed. CMA revealed a run of homozygosity (ROH) at 2q33.1. WES identified a homozygous deletion encompassing exons 24–25 of ALS2 , inherited from heterozygous parents. This clinical phenotype was consistent with the IAHSP spectrum , and no previous cases due to intragenic deletion have been reported. Our findings further expand the mutational spectrum of ALS2 ‐related disorders and underscore the relevance of combining CMA and WES in the diagnostic workup of early‐onset motor disorders, particularly in consanguineous families and unresolved cases. Greater awareness of rare intragenic deletions may improve early recognition and facilitate accurate genetic counseling in pediatric neurogenetics.
Journals
2026 EN
Banaszak Lauren G. · Fiala Elise · CeyhanBirsoy Ozge
+13 more
ABSTRACT RTEL1 R1264H is a founder variant with a carrier frequency of 0.3%–1.0% in the Ashkenazi Jewish population. While biallelic RTEL1 R1264H causes a severe form of telomere biology disorder (TBD) presenting in childhood, the clinical significance of monoallelic carrier status has remained uncertain, limiting effective counseling and management. Here, we describe the clinical features, telomere lengths, and tumor somatic profiles of cancer patients found to be heterozygous for RTEL1 R1264H to evaluate for evidence of subclinical TBD in this population. Among 39,337 individuals who underwent RTEL1 germline analysis via MSK‐IMPACT, 32 (0.08%) were incidentally found to be heterozygous for RTEL1 R1264H. Three individuals (9%) met diagnostic criteria for TBD based on compatible clinical features and telomere shortening, and two additional individuals (6%) had histories suspicious for TBD but did not have telomere length data available. Notably, 7 individuals (22%) experienced severe or fatal therapy‐related toxicities, despite many lacking other clinical features of a TBD. These findings support that RTEL1 R1264H can act in an autosomal dominant fashion and confer TBD disease risk, albeit with low penetrance, and may increase susceptibility to treatment‐related complications.
Journals
2026 EN
Ajmone Paola Francesca · Rigamonti Claudia · Brasca Francesca
+6 more
ABSTRACT Pathogenic variants in the non‐coding spliceosomal gene RNU4‐2 underlie ReNU syndrome, one of the most prevalent monogenic causes of neurodevelopmental disorders, accounting for ~0.4% of cases. Despite increasing recognition, little is known about the longitudinal behavioral and neuropsychiatric phenotype of affected individuals. We report two patients with RNU4‐2 variants, providing a comprehensive description of their developmental trajectories from infancy to adolescence. Both exhibited global developmental delay, impaired adaptive functioning, and significant language deficits. Distinctive features included persistent attention deficits and Autistic Spectrum Disorder, which emerged as hallmarks of the Syndrome. Case‐specific differences were notable: one patient developed self‐injurious behavior and social anxiety during adolescence, while the other presented with epilepsy and structural brain anomalies. Neuroimaging revealed convergent features, including white matter reduction, corpus callosum thinning, and ventricular dysmorphisms. Our findings highlight the importance of early, individualized interventions, with particular emphasis on augmentative and alternative communication strategies and cognitive‐behavioral approaches to mitigate communicative frustration, behavioral dysregulation, and social anxiety. This study provides the first longitudinal neuropsychiatric characterization of RNU4‐2‐related disorder, delineating clinical hallmarks, and therapeutic windows. A better understanding of developmental trajectories in this condition is essential to optimize patient management and improve long‐term outcomes.
Journals
2026 EN
Strekalova Sofia O. · Koov Alexander I. · Khvorova Maria A.
+7 more
ABSTRACT N‐Aryl phenothiazines are privileged scaffolds in materials science and medicinal chemistry, yet their synthesis often relies on transition metals or stoichiometric oxidants. Herein, we report a sustainable, metal‐free electrochemical (EC) method for the C–H amination of phenols and anilines with phenothiazines. This protocol employs stable platinum electrodes under mild, oxidant‐free conditions, enabling the late‐stage functionalization of pharmaceuticals and natural products with high efficiency (up to 97% yield) and excellent regioselectivity. Furthermore, we introduce a complementary photoelectrochemical (PEC) strategy that, for a subset of substrates, provides superior yields, including several near‐quantitative transformations. Mechanistic studies via cyclic voltammetry and EPR spectroscopy confirm the generation of a persistent phenothiazine radical cation (PTZ• + ) as the key electrophilic intermediate. The efficiency of both EC and PEC pathways is rationalized by the stability of these radical cations, which is tunable by substituent effects.
Journals
2026 EN
AliagaSamanez Gabriela · Gestich Carla · AyalaBurbano Paola Andrea
+9 more
ABSTRACT Allochthonous species can negatively impact biodiversity by introducing new pathogens, intensifying competition for resources, promoting habitat changes, and causing ecosystem disruption. Introduced species can also spread into areas designated for the conservation of native species. This colonization and, eventually, contact between historically isolated lineages can cause hybridization, resulting in decreased offspring fitness or, conversely, promoting hybrid vigor, threatening the integrity of native populations and increasing their risk of extinction. Here, we analyzed an allochthonous population from a fragment of Brazilian Atlantic Forest, where both endangered Golden‐headed lion tamarins and Golden lion tamarins were illegally introduced into the natural range of the Golden lion tamarin in the 1990s. We performed Genotyping by Sequencing and complementary mitochondrial analysis to investigate hybridization and to assess the genetic diversity and structure of the invasive population. Our results were able to rule out the existence of hybrids among the samples analyzed, providing relevant information about the genetic diversity of the alien population and effectively contributing to conservation programs and management actions for both species. Conservation actions and effective surveillance policies to prevent new illegal introductions should be mandatory to ensure the protection of these threatened charismatic species which are targets of illegal trade and trafficking.
Journals
2026 EN
Manzano Maria Carolina Rodella · Sawaya Ricardo J. · Rezende Gabriela Cabral
+1 more
ABSTRACT Acoustic communication is important for social cohesion and territory defense in forest primates, including the endangered lion tamarins (genus Leontopithecus ). Although vocalizations of individual species have been studied, there is still no comparative analysis examining whether acoustic parameters can reliably distinguish among all four species. We hypothesized that species‐specific differences in acoustic features allow discrimination among lion tamarin species, and we predicted that both spectral and temporal parameters would reveal interspecific variation. To test this, we analyzed seven shared vocalizations (long calls, whines, trills, rasps, clucks, tsicks, and peeps) from the black‐faced lion tamarin ( Leontopithecus caissara ), golden lion tamarin ( Leontopithecus rosalia ), golden‐headed lion tamarin ( Leontopithecus chrysomelas ), and black lion tamarin ( Leontopithecus chrysopygus ). Acoustic data were obtained from online sound libraries and analyzed using Raven Pro software. Spectral and temporal parameters, including frequency at 5% and 95%, peak frequency, center frequency, and bandwidth 90% were measured, followed by principal component analysis (PCA) and nonparametric statistical tests to identify species‐specific differences. Our results revealed significant interspecific differences across multiple vocalizations, with spectral parameters being the most relevant for distinguishing species, whereas temporal parameters contributed less. L. caissara emerged as the most acoustically distinct species, while L. rosalia and L. chrysopygus exhibited the greatest vocal similarity. In conclusion, this study provides the first comparative analysis of seven vocalization types across all four lion tamarin species, establishing an acoustic baseline, confirming the importance of spectral parameters for species differentiation, and demonstrating the potential of vocalizations for conservation applications.