Optimizing genomic DNA extraction from long-term preserved formalin-fixed and paraffin-embedded lung cancer and lymph node tissues.

Personalized therapy in lung cancer (LC) has revolutionized routine histopathology and cytopathology, emphasizing the importance of obtaining adequate material for molecular studies to support oncological decisions. Adaptations of cytologic sample preparations offer benefits for molecular testing, yet their potential remains underutilized. A significant number of LC cases is identified through specimens of aspiration or exfoliative cytology.

Methylation assay in KMT2B-related dystonia: a novel diagnostic validation tool.

Background/objectives: KMT2B-related dystonia (DYT28, OMIM #617284) is a progressive neurological condition characterized by early onset movement disorders with autosomal dominant inheritance. In this study, we describe the use of a genome methylation episignature methodology to functionally validate two variants of uncertain significance (VUS) in the KMT2B gene.

Methods: Genome-wide methylation status was assessed using the EPIC methylation assay in peripheral blood samples from two subjects with early onset movement disorder and missense variants of uncertain significance in the KMT2B gene (p.

Neuropsychological Profile of 25 Brazilian Patients with 22q11.2 Deletion Syndrome: Effects of Clinical and Socioeconomic Variables.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with a heterogeneous neurocognitive phenotype, which includes psychiatric disorders.

Post-COVID-19 condition: systemic inflammation and low functional exercise capacity.

Introduction: Post-COVID-19 condition (PCC) is characterised by a plethora of symptoms, with fatigue appearing as the most frequently reported. The alterations that drive both the persistent and post-acute disease newly acquired symptoms are not yet fully described. Given the lack of robust knowledge regarding the mechanisms of PCC we have examined the impact of inflammation in PCC, by evaluating serum cytokine profile and its potential involvement in inducing the different symptoms reported.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.

Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank.

The interaction between polygenic risk score and trauma affects the likelihood of post-traumatic stress disorder in female victims of sexual assault.

Objective: Post-traumatic stress disorder (PTSD) is triggered by traumatic events, but genetic vulnerability and a history of childhood trauma may also increase the risk of PTSD onset. Thus, we investigated the interaction between genetic susceptibility according to polygenic risk score (PRS), and traumatic events.

Methods: We evaluated 68 women with PTSD who had been sexually assaulted and 63 healthy controls with no history of sexual assault.

Diffuse hemispheric glioma with H3 p.K28M (K27M) mutation: Unusual non-midline presentation of diffuse midline glioma, H3 K27M-altered?

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.

Cytogenetics investigation in 151 Brazilian infertile male patients and genomic analysis in selected cases: experience of 14 years in a public genetic service.

Objectives: Male infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for the adequate clinical management of these patients. We aimed to conduct a cytogenetic investigation of numerical and structural rearrangements and a genomic study of Y chromosome microdeletions/microduplications in infertile men derived from a single centre with over 14 years of experience.

Establishment and Comprehensive Molecular Characterization of an Immortalized Glioblastoma Cell Line from a Brazilian Patient.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with few effective treatment strategies. The research on the development of new treatments is often constrained by the limitations of preclinical models, which fail to accurately replicate the disease's essential characteristics. Herein, we describe the obtention, molecular, and functional characterization of the GBM33 cell line.

Strong OLIG2 expression in supratentorial ependymoma, ZFTA fusion-positive: A potential diagnostic pitfall.

Ependymomas (EPN) are central nervous system neoplasms that exhibit an ependymal phenotype. In particular, supratentorial EPN (ST-EPN) must be differentiated from more aggressive entities such as glioblastoma, IDH-wildtype. This task is frequently addressed with the use of immunohistochemistry coupled with clinical presentation and morphological features.

DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients.

Objective: Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence.

SIN3A Defects Associated with Syndromic Congenital Hypogonadotropic Hypogonadism: An Overlap with Witteveen-Kolk Syndrome.

Introduction: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition caused by GnRH deficiency. More than 40 genes have been associated with the pathogenesis of CHH, but most cases still remain without a molecular diagnosis. Mutations involving the same gene (e.

Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p.

Introduction: Cri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to confirm deletions in the short arm of chromosome 5 (5p-) greater than 10 Mb. In cases of smaller deletions, it is necessary to resort to other molecular techniques such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA) or genomic array.

Identifying Genetic Etiology in Patients with Intellectual Disability: An Experience in Public Health Services in Northeastern Brazil.

Intellectual disability (ID) is considered a common neuropsychiatric disorder that affects up to 3% of the population. The etiologic origin of ID may be genetic, environmental, and multifactorial. Chromosomopathies are relatively common among the genetic causes of ID, especially in the most severe cases and those associated with dysmorphic features.

Comparison of intravenous and inhalation anesthesia on postoperative behavior changes in children undergoing ambulatory endoscopic procedures: A randomized clinical trial.

Background: Early and delayed behavioral changes are well recognized after anesthesia. Intravenous anesthesia may prevent emergence delirium. However, it has not been evaluated as a preventive strategy for delayed postoperative behavior changes.

Expanding the Phenotype of 8p23.1 Deletion Syndrome: Eight New Cases Resembling the Clinical Spectrum of 22q11.2 Microdeletion.

Objective: To report the effectiveness of early molecular diagnosis in the clinical management of rare diseases, presenting 8 patients with 8p23.1DS who have clinical features that overlap the phenotypic spectrum of 22q11.2DS.

Progression of Type 1 Diabetes: Circulating MicroRNA Expression Profiles Changes from Preclinical to Overt Disease.

Objectives: To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D.

Methods: We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group).

Results: The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls.

The Location of Disease-Causing DES Variants Determines the Severity of Phenotype and the Morphology of Sarcoplasmic Aggregates.

Desmin (DES) is the main intermediate muscle filament that connects myofibrils individually and with the nucleus, sarcolemma, and organelles. Pathogenic variants of DES cause desminopathy, a disorder affecting the heart and skeletal muscles. We aimed to analyze the clinical features, morphology, and distribution of desmin aggregates in skeletal muscle biopsies of patients with desminopathy and to correlate these findings with the type and location of disease-causing DES variants.

Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p- syndrome.

Objectives: Copy Number Variations (CNVs) in the human genome account for common populational variations but can also be responsible for genetic syndromes depending on the affected region. Although a deletion in 5p is responsible for a syndrome with highly recognizable phenotypical features, other chromosomal abnormalities might overlap phenotypes, especially considering that most studies in 5p use traditional cytogenetic techniques and not molecular techniques.

Methods: The authors have investigated 29 patients with clinical suspicion of 5p- syndrome using Chromosomal Microarray (CMA), and have gathered information on previous tests, clinical signs, symptoms, and development of the patients.

The complex search for the cause of gastroschisis.

Background: To reveal the complex etiology of gastroschisis through two independent cases.

Cases: Case 1 involves gastroschisis recurrence in a consanguineous marriage, and Case 2 concerns a fetus with gastroschisis whose mother had undergone gastroplasty. Methylation array was carried out in both cases (two fetuses with gastroschisis, their two mothers, one father from the consanguineous marriage), and in 16 controls (fetuses and their respective mothers).