Case Report: Unmasking the role of rem sleep in modulating non-convulsive status epilepticus in ring chromosome 20 syndrome: a genetic disorder of sleep architecture?

Ring chromosome 20 syndrome (r (20)) is a rare genetic disorder characterized by drug-resistant epilepsy, cognitive impairment, and behavioral changes, often manifesting with non-convulsive status epilepticus (NCSE). We report a unique case of a 38-year-old woman with r (20) and recurrent NCSE, demonstrating a novel and striking electro-clinical correlation. Continuous video-EEG monitoring revealed distinct, alternating electro-clinical phases, with NCSE manifesting as continuous spike-wave during sleep (CSWS)-like patterns.

Clinical course and management challenges in Lafora disease: a narrative analysis in an Apulian cohort.

Background: Lafora disease (LD) is an ultra-rare, autosomal recessive neurodegenerative disorder characterized by the accumulation of Lafora bodies in the brain, leading to drug-resistant epilepsy, myoclonus, progressive dementia, and cerebellar dysfunction. This retrospective study describes the clinical course and management challenges of LD in a cohort of patients from the Apulia region of Southern Italy, where the disease prevalence appears to be higher than in other populations.

Methods: We retrospectively analyzed clinical, electroencephalographic, and management data from six unrelated families with a confirmed diagnosis of LD, followed at the Neurology Unit of the Scientific Institute Casa Sollievo della Sofferenza Hospital between 2010 and 2024.

Integrated Genomic Approach: A Five Exon Intragenic Deletion in UNC80 Combines With a Novel Splice Variant to Cause IHPRF2 Syndrome in an Italian Family.

Rare diseases impact ~6%-8% of the population, thus constituting an issue for public health worldwide. The increasing application of genomic technologies in the routine diagnosis of these conditions is documenting the need to integrate multiple techniques in the most complex cases. We describe a 14-year-old boy and his 4-year-old sister, both presenting with neonatal hypotonia, severe global developmental delay, major feeding difficulties with the need for assisted nutrition, inability to speak and walk autonomously, epilepsy, central sleep apnea, and facial dysmorphism, in whom exome sequencing revealed the novel c.

Generation of a human induced pluripotent stem cell line (CIBIOi007-A) from a Lafora disease patient.

An induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) of a 24-year-old male patient affected by Lafora disease. The patient is homozygous for the c.721C>T, p.

Variant sub-tiering, disease-gene associations and strictness of clinical criteria improves the interpretation of variants of uncertain significance in hereditary cardiomyopathies and rhythm disorders.

Besides the ClinGen's efforts to standardize the ACMG/AMP criteria and European initiatives aimed at monitoring quality standards, molecular diagnostics of hereditary cardiomyopathies and heart rhythm disorders (HCHRDs) remains strongly influenced by the local strategies developed to overcome the variables in which genetic testing is requested. This is a monocentric study on the clinical and molecular findings of 363 pedigrees with various HCHRDs. ACMG/AMP criteria were adapted according to the ClinGen's material and internal specifications.

Long-Term Phenotypic Evolution in GRIN2A-Related Disorders: Electroclinical and Genetic Insights from Two Families with Extended Follow-Up.

The gene and its product protein have been linked to a wide spectrum of neurodevelopmental disorders named -related disorders. Clinical presentation is highly variable and characteristically includes acquired cognitive, behavioral, and language impairment, as well as epilepsy, ranging from benign forms to severe epileptic encephalopathy. Recent genetic investigations have expanded the clinical spectrum of heterozygous variants, improving our understanding of genotype-phenotype correlations.

Gonadal Mosaicism for an ASH1L Intragenic Deletion Makes a Bridge Between MRD52 and 1q22 Microdeletion.

ASH1L gene encodes a histone lysine methyltransferase, highly expressed in both embryonic and adult human brain. De novo loss-of-function variants in ASH1L are described in an ultrarare monogenic neurodevelopmental disorder, previously called mental retardation type 52 (MRD52). At the same time, a few cases are reported in the literature and DECIPHER with 1q22 microdeletions spanning ASH1L.

Phenotypic Description of A Patient with ODLURO Syndrome and Functional Characterization of the Pathogenetic Role of A Synonymous Variant c.186G>A in Gene.

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant disorder caused by mutations in the gene. The clinical phonotype of the affected individuals is typically characterized by global developmental delay, autism, epilepsy, hypotonia, macrocephaly, and very mild dysmorphic facial features. In this report, we describe the case of a 6-year-old boy with ODLURO syndrome who is a carrier of the synonymous mutation c.

Identification of a Novel Variant in a Patient with Hypotonia, Intellectual Disability, and Severe Speech Impairment.

The FOXP subfamily includes four different transcription factors: FOXP1, FOXP2, FOXP3, and FOXP4, all with important roles in regulating gene expression from early development through adulthood. Haploinsufficiency of , due to deleterious variants (point mutations, copy number variants) disrupting the gene, leads to an emerging disorder known as " syndrome", mainly characterized by intellectual disability, language impairment, dysmorphic features, and multiple congenital abnormalities with or without autistic features in some affected individuals (MIM 613670). Here we describe a 10-year-old female patient, born to unrelated parents, showing hypotonia, intellectual disability, and severe language delay.

Different states of stemness of glioblastoma stem cells sustain glioblastoma subtypes indicating novel clinical biomarkers and high-efficacy customized therapies.

Background: Glioblastoma (GBM) is the most malignant among gliomas with an inevitable lethal outcome. The elucidation of the physiology and regulation of this tumor is mandatory to unravel novel target and effective therapeutics. Emerging concepts show that the minor subset of glioblastoma stem cells (GSCs) accounts for tumorigenicity, representing the true target for innovative therapies in GBM.

Co-occurrence of Beckwith-Wiedemann syndrome and pseudohypoparathyroidism type 1B: coincidence or common molecular mechanism?

Imprinting disorders are congenital diseases caused by dysregulation of genomic imprinting, affecting growth, neurocognitive development, metabolism and cancer predisposition. Overlapping clinical features are often observed among this group of diseases. In rare cases, two fully expressed imprinting disorders may coexist in the same patient.

Association of CSF and PET markers of neurodegeneration with electroclinical progression in Lafora disease.

Purpose: To evaluate the electro-clinical features in association with laboratory and instrumental correlates of neurodegeneration to detect the progression of Lafora disease (LD).

Methods: We investigated the electro-clinical longitudinal data and CSF Aβ42, p-tau and t-tauAg, amyloid, and F-FDG PET of five unrelated LD families.

Results: Three progressive electro-clinical stages were identified.

What Have We Learned from Patients Who Have Arboleda-Tham Syndrome Due to a De Novo Pathogenic Variant with Impaired Histone Acetyltransferase Function? A Precise Clinical Description May Be Critical for Genetic Testing Approach and Final Diagnosis.

Pathogenic variants in genes are involved in histone acetylation and deacetylation resulting in congenital anomalies, with most patients displaying a neurodevelopmental disorder and dysmorphism. Arboleda-Tham syndrome caused by pathogenic variants in KAT6A (Lysine Acetyltransferase 6A; OMIM 601408) has been recently described as a new neurodevelopmental disorder. Herein, we describe a patient characterized by complex phenotype subsequently diagnosed using the clinical exome sequencing (CES) with Arboleda-Tham syndrome (ARTHS; OMIM 616268).

A t(4;13)(q21;q14) translocation in B-cell chronic lymphocytic leukemia causing concomitant homozygous DLEU2/miR15a/miR16-1 and heterozygous ARHGAP24 deletions.

13q14 deletion is the most recurrent chromosomal aberration reported in B-CLL, having a favorable prognostic significance when occurring as the sole cytogenetic alteration. However, its clinical outcome is also related to the deletion size and number of cells with the del(13)(q14) deletion. In 10% of cases, 13q14 deletion arises following a translocation event with multiple partner chromosomes, whose oncogenic impact has not been investigated so far due to the assumption of a possible role as a passenger mutation.

miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response.

Locally advanced non-small cell lung cancer (NSCLC) is frequent at diagnosis and requires multimodal treatment approaches. Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for operable locally advanced NSCLC (Stage IIIA). However, the majority of patients are NACT-resistant and show persistent lymph nodal metastases (LNmets) and an adverse outcome.

Extracellular vesicle microRNAs contribute to Notch signaling pathway in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive T-cell malignancy characterized by genotypically-defined and phenotypically divergent cell populations, governed by adaptive landscapes. Clonal expansions are associated to genetic and epigenetic events, and modulation of external stimuli that affect the hierarchical structure of subclones and support the dynamics of leukemic subsets. Recently, small extracellular vesicles (sEV) such as exosomes were also shown to play a role in leukemia.

Electro-clinical features and management of the late stage of Lafora disease.

Purpose: The aim of this study was to elucidate the electro-clinical features and management of the late stage of Lafora disease (LD).

Methods: We investigated the electro-clinical data and medical complications of three LD patients with mutations in and two in genes during the LD late stage.

Results: The late stage emerged after a mean period of 7 ± 1.

Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances.

Background: Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively.

Growth factor independence underpins a paroxysmal, aggressive Wnt5a/EphA2 phenotype in glioblastoma stem cells, conducive to experimental combinatorial therapy.

Background: Glioblastoma multiforme (GBM) is an incurable tumor, with a median survival rate of only 14-15 months. Along with heterogeneity and unregulated growth, a central matter in dealing with GBMs is cell invasiveness. Thus, improving prognosis requires finding new agents to inhibit key multiple pathways, even simultaneously.

Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism.

The circadian gene Timeless (TIM) provides a molecular bridge between circadian and cell cycle/DNA replication regulatory systems and has been recently involved in human cancer development and progression. However, its functional role in colorectal cancer (CRC), the third leading cause of cancer-related deaths worldwide, has not been fully clarified yet. Here, the analysis of two independent CRC patient cohorts (total 1159 samples) reveals that loss of TIM expression is an unfavorable prognostic factor significantly correlated with advanced tumor stage, metastatic spreading, and microsatellite stability status.

Loss-of-function variants in exon 4 of TAB2 cause a recognizable multisystem disorder with cardiovascular, facial, cutaneous, and musculoskeletal involvement.

Purpose: This study aimed to describe a multisystemic disorder featuring cardiovascular, facial, musculoskeletal, and cutaneous anomalies caused by heterozygous loss-of-function variants in TAB2.

Methods: Affected individuals were analyzed by next-generation technologies and genomic array. The presumed loss-of-function effect of identified variants was assessed by luciferase assay in cells transiently expressing TAB2 deleterious alleles.