One of the multifactorial pregnancy-specific disorders that has a serious impact on maternal and perinatal morbidity is preeclampsia (PE). Long noncoding RNAs (lncRNAs), such as GAS5 and H19, have been shown in recent research to play a regulatory function in placental development and the pathophysiology of PE. To determine the diagnostic association between the lncRNAs GAS5 and H19 and PE, this study compared the expression levels of these lncRNAs in the serum of pregnant women with mild and severe PE and normotensive pregnant controls. A total of 195 pregnant women who visited the Obstetrics and Gynecology Department at Menoufia University Hospital between September 2023 and October 2025 participated in this case-control study. They were classified into three equal groups: normotensive pregnant women (control group, n = 65), mild PE (n = 65), and severe PE (n = 65). The levels of GAS5 and H19 expression in serum samples were assessed using quantitative real-time PCR. Compared with controls, both the mild and severe PE groups showed significantly higher GAS5 expression and significantly lower H19 expression. Nevertheless, there was no obvious distinction in GAS5 and H19 levels between mild and severe PE. The ROC curve analysis demonstrated that GAS5 had high sensitivity and specificity for distinguishing PE from normal pregnancy. The dysregulation of GAS5 and H19 may contribute to the pathogenesis of PE. GAS5, in particular, demonstrates promising potential as a noninvasive biomarker for PE. GAS5 and H19 do not discriminate between PE severity levels.

Incurable hereditary diseases such as Duchenne muscular dystrophy (DMD), Huntington's disease (HD), and myotonic dystrophy type 1 (DM1) fall into the nucleotide repeat expansion disorder (NRED) category. The discovery of CRISPR-Cas genome editing has paved the way toward hopeful strategies for accurate DNA-level repair. This systematic review presents preclinical data on the efficacy, molecular effects, and limitations of CRISPR-based treatments for NREDs. As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, systematic PubMed, Scopus, and Embase searches up to June 2025 identified studies that evaluated CRISPR-Cas systems in human-derived in vitro models of NREDs. Methodological Index for Non-Randomized Studies tool was used to score eligible studies by methodological quality. CRISPR platforms, delivery systems, gene targets, molecular endpoints, and functional rescue data were extracted and synthesized descriptively. Twenty-four out of 6510 records screened were included. They employed most of them to target specific DMD (n = 9), HD (n = 6), and DM1 (n = 3) with patient-derived induced pluripotent stem cells or differentiated myogenic/neuronal cells. Streptococcus pyogenes CRISPR-associated protein 9 as a nuclease was the most frequently used, although engineered Cas9 enzymes and dCas9 fusion proteins were also utilized to control transcription. Delivery was achieved through viral vectors (adeno-associated virus, lentivirus) and nonviral routes (plasmid, lipofection, electroporation). Uniform genomic editing, transcript rescue, and protein restoration were seen in CRISPR-mediated editing studies, and functional restoration was demonstrated for splicing correction and dystrophin restoration. Methodological flaws such as the absence of blinding, failure to follow up, and lack of full reporting of off-target effects limited robustness. CRISPR-Cas systems exhibit reproducible molecular and functional correction in NRED models with their translational potential. Methodological strength, whole safety profiling, and invivo verification remain a necessity, however, before clinical translation.

Family with sequence similarity 216 member A (FAM216A) is overexpressed in several cancer tissues, but its prognostic value and pathological effect in hepatocellular carcinoma (HCC) have not been fully elucidated. FAM216A expression in HCC specimens and cell lines was determined by real-time PCR and western blotting. FAM216A expression was knocked down in HCCLM3 and Huh7 cells, and overexpressed in Hep3B and PLC/PRF/5 cells. The proliferation, migration, and invasion of different HCC cell lines were assessed by colony formation and Transwell assays. The expression of epithelial-mesenchymal transition (EMT)-related proteins and the level of polo-like kinase 1/extracellular regulated protein kinase (PLK1/ERK) were determined. Increased FAM216A expression was observed in HCC tissues, a result that is consistent with outcomes obtained from an online database, and patient prognosis was negatively correlated with the FAM216A expression level. Additionally, FAM216A overexpression promoted the proliferation, migration, and invasion of HCC cells and activated EMT via the PLK1/ERK signaling pathway. FAM216A is overexpressed in HCC tissues and is associated with poor clinical outcomes. Mechanistically, FAM216A promotes aggressive tumor behavior by activating the PLK1/ERK signaling pathway.

X-linked female-limited high myopia (MYP26, OMIM:301010) is a rare Mendelian subtype of early-onset high myopia (eoHM), with females having progressive myopic refractive error (≥-6 D) and males as asymptomatic carriers. Pathogenic variants in ARR3 (OMIM:301770) have been linked to eoHM, but the spectrum of ARR3 variants in Chinese populations remains incompletely defined. To identify the causative variant in a Chinese eoHM family and expand ARR3 variant spectrum for MYP26. We conducted clinical and genetic analyses of a Chinese family with eoHM. The proband underwent clinical examinations and whole-exome sequencing (WES). Sanger sequencing validated variants in affected family members, and bioinformatics tools evaluated variant pathogenicity. WES identified an ARR3 c.214C>T (p.R72X) stop-gain variant, co-segregating with the disease phenotype and predicted to truncate cone arrestin, disrupting phototransduction. A female carrier showing incomplete penetrance (I-1) was identified, which highlights the unrecognized complexity of the pathogenic mechanism underlying MYP26. This variant was first reported in the Chinese population. Our study expands the ARR3 variant spectrum associated with eoHM, highlighting the role of ARR3 c.214C>T (p.R72X), first reported in Chinese populations. The finding of incomplete penetrance underscores the complexity of X-linked female-limited inheritance and provides a reference for genetic counseling of related families.

Red blood cell (RBC) membranopathies, caused by genetic alterations in membrane and cytoskeletal proteins, lead to significant variability in clinical presentation. This study analyzes 23 single nucleotide variants across nine genes (ADD1, ADD2, ANK1, EPB41, PIEZO1, SLC4A1, SPTA1, SPTB, and TAF3) in 225 Mexican patients with suspected RBC membranopathies and their effects on hematological parameters. Key variants, such as ADD2:c.1797C>T, SPTA1:c.5992G>C, SPTA1:c.6046C>A and SPTA1:c.6531-12C>T, were significantly associated with decreased RBC count, hemoglobin levels, packed cell volume, mean corpuscular hemoglobin and/or mean corpuscular hemoglobin concentration. Additionally, the following six combinations showed significant associations with two or three hematological parameters: SPTA1:c.5992G>C + SPTA1:c.6046C>A, SPTA1:c.5992G>C + ADD1:c.1378G>T, ADD1:c.1378G>T + ADD2:c.1797C>T, ADD1:c.1378G>T + PIEZO1:c.6793A>G, ADD2:c.1797C>T + PIEZO1:c.6793A>G, and TAF3:c.410-2550A>G + SPTA1:c.6531-12C>T. These findings underscore the importance of selected population genetic studies to increase our understanding of genotype-hematological phenotype relationships in RBC membranopathies.

Major depressive disorder (MDD) is a prevalent and disabling psychiatric condition in Saudi Arabia, with genetic susceptibility remaining incompletely characterized. Reduced brain-derived neurotrophic factor (BDNF) activity has been implicated in MDD. The Val66Met polymorphism (rs6265), involving the substitution of valine (Val, G allele) with methionine (Met, A allele), impairs activity-dependent BDNF secretion. This study examined the frequency of Val66Met and its association with MDD in a Saudi cohort. A case-control study was conducted, including 87 patients with MDD (44 males, 43 females; mean age 44.2 ± 11.5 years) and 87 healthy controls (39 males, 48 females; mean age 28.7 ± 8.4 years). Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Unadjusted and age- and sex-adjusted logistic regression analyses were applied under genotype-specific, dominant, recessive, and allelic models. The Val/Val (GG) genotype was more frequent in controls than patients (54.0% vs. 34.5%), whereas the Met/Met (AA) genotype was detected exclusively in patients (21.8% vs. 0%; χ2 = 22.80, p = 1.1 × 10-5). The Met (A) allele frequency was significantly higher in patients (43.7% vs. 23.0%; χ2 = 15.84, p = 6.9 × 10-5). Unadjusted analysis showed a protective effect of GG (OR = 0.45, 95% CI: 0.24-0.82) and a markedly increased risk associated with AA (OR = 49.81, 95% CI: 2.95-839.90). Dominant carriers (GA + AA) had increased odds of MDD (OR = 2.23), and each A allele conferred a higher risk (OR = 2.60). These associations remained significant after adjustment for age and sex. The BDNF Val66Met polymorphism is associated with MDD susceptibility in Saudis. The Met (A) allele, particularly in homozygosity, confers increased risk, while the Val/Val genotype appears protective, supporting population-specific genetic contributions to depression.

Although several approaches have identified individual genes that contribute to autism spectrum disorder (ASD), more research is needed to establish whether these single nucleotide polymorphisms are associated with a lower risk. Studies have found that the oxytocin receptor (OXTR) and arginine-vasopressin receptors (AVPR) genes have an essential role as neuromodulators or neurotransmitters in ASD. Most of these studies have been primarily carried out in the United States, Western Europe, and Australasia, and there is divergence in the conclusions. To date, there are no existing studies in Mexico on the possible usefulness of these genes as biomarkers; hence, this study analyzes the association of the rs2254298 in the OXTR1, rs7294536 in the AVPR1a, and rs28632197 in the AVPR1b with ASD. Seventy-five samples of children with ASD and 71 samples corresponding to children with neurotypical development were analyzed. The study found a robust protective association for A allele of the rs28632197 in the AVPR1b, while no effect was found for the rs2254298 and rs7294536. The importance of these findings is that the protective association can prevent the disorder from occurring or prevent a more severe manifestation. These findings open new avenues for research in the role played by gene-environment interaction in different geographical and ethnic populations.

Background: Postaxial polydactyly (PAP) is characterized by the development of extra digits at the fifth finger. It can occur as an isolated disease or a part of a syndrome. The genetic basis of nonsyndromic PAP has been linked to sequence variants in different genes. The aim of the present study was to identify the causative genetic variants in four Pakistani families demonstrating PAP. Methods: Causative genetic variants were identified using whole-exome sequencing and microsatellite mapping, followed by validation through Sanger sequencing. Further analysis was carried out through conservation, structural modeling, and 100-ns molecular dynamic simulations of GLI1. Results: Whole-exome and targeted sequencing in four families (A, B, C, and D) identified novel variants in the GLI1 (c.1013G>T; p.Cys338Phe), and GLI3 (c.2003C>T; p.Pro668Leu and c.4564delG; p.Ala1522ProfsTer2), and a recurrent variant in IQCE genes (c.895_904del; p.Val301SerfsTer8) linked to 7p22.3. All the variants were highly conserved across different species. Comparative analysis of the GLI1WT and GLI1Cys338Phe proteins revealed domain fluctuations leading to the loss of structurally and functionally important inter- and intramolecular interactions. The three-dimensional structural analysis of the GLI3 protein showed that the missense variant p. (Pro668Leu) disturbed the protein folding and intra-residue interaction, while the frameshift variant p. (Ala1522ProfsTer2) led to the loss of the C-terminus of the protein. Similarly, the IQCE structural analysis confirmed the loss of protein function due to frameshift and C-terminal deletion. Conclusion: This study has broadened the phenotypic and allelic spectrum of the genes associated with isolated PAP and strengthened the role of these genes in regulating limb development.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory disorder responsible for the global pandemic and widespread mortality. Circular RNAs (circRNAs), one of the newest forms of noncoding RNAs (ncRNAs), are important regulators of the host immune response and viral replication through sponging of microRNAs (miRNAs). This work aims to look at the expression and functions of hsa_circ_0009910/hsa-miR-145-5p/IFN beta 1 (IFNB1) in SARS-CoV-2-related infection and the molecular mechanisms that underpin them. In the experimental phase of the study, total RNA was isolated from the peripheral blood mononuclear cells (PBMCs) of 48 patients with symptomatic COVID-19, 48 patients with nonsymptomatic COVID-19, and 48 negative controls, and then cDNA was synthesized. Next, the expression of these genes was examined with quantitative real-time PCR (qRT-PCR). A receiver operating characteristic (ROC) curve was created to assess each gene's potential as a biomarker. The interactions of hsa_circ_0009910, hsa-miR-145-5p, and IFNB1, also the functional and pathway enrichment analyses, were detected by bioinformatics analysis. When compared with the negative control group, the expression of hsa_circ_0009910 in both symptomatic and nonsymptomatic groups, and IFNB1 in the symptomatic group was higher in the COVID-19 patients. Furthermore, the relative expression of hsa-miR-145-5p in the symptomatic and nonsymptomatic groups was lower than that in the negative control group. In addition, there was a positive correlation between hsa_circ_0009910 and IFNB1 expression, as well as a negative correlation between hsa-miR-145-5p, hsa_circ_0009910, and IFNB1 expressions. hsa-miR-145-5p has a higher area under the curve and may be a more effective biomarker to distinguish COVID-19 patients from the healthy controls, based on ROC curve study, but further study is needed. In conclusion, our data show that the hsa_circ_0009910/hsa-miR-145-5p/IFNB1 triple network may play a role in the pathogenesis of COVID-19 and can be considered a therapeutic target in COVID-19 patients.