Genetic Disorders Research Articles

In Search of Spinal Muscular Atrophy Disease Modifiers

The 5q Spinal Muscular Atrophy (SMA) is a hereditary autosomal recessive disease caused by defects in the survival motor neuron (SMN1) gene encoding survival motor neuron (SMN) protein. Currently, it is the leading cause of infantile mortality worldwide. SMA is a progressive neurodegenerative disease with “continuum of clinical severity”, which can be modulated by genetic and epigenetic factors known as disease modifiers (DMs). Individuals (even siblings) with the same defects in SMN1 gene might have strikingly different types of SMA, supposedly due to the impact of DMs. There are several therapeutic options for SMA, all of them focusing on the restoration of the SMN protein levels to normal. Determining DMs and the pathways in which they are involved might aid in enhancing existing curative approaches. Furthermore, DMs might become novel therapeutic targets or prognostic biomarkers of the disease. This narrative review provides a brief overview of the genetics and pathobiology of SMA, and its bona fide modifiers. We describe novel, emerging DMs, approaches and tools used to identify them, as well as their potential mechanisms of action and impact on disease severity. We also propose several disease-modifying molecular mechanisms which could provide a partial explanation of the staggering variability of SMA phenotypes.

Red blood cell alloimmunization in transfused patients with hereditary hemorrhagic telangiectasia: A single centre retrospective study

BackgroundHereditary hemorrhagic telangiectasia (HHT) is a genetic blood vessel disorder which may lead to chronic bleeding and red blood cell (RBC) transfusions. Data on transfusion requirements and complications in HHT patients are sparse. Study Design and MethodsRetrospective chart review was conducted at St. Michael’s Hospital (SMH) in Toronto, Canada. All adults with a definite clinical diagnosis of HHT AND inpatient hospital visits between January 1, 2011 and December 31, 2020 AND had undergone transfusion compatibility testing at SMH, were identified. Data were abstracted from electronic medical records. Simple descriptive statistics were used to analyze data. Institutional Research Ethics Board approval was obtained. Results63 HHT patients underwent compatibility testing and were subsequently transfused at SMH. Median patient age at data abstraction was 70 years (Interquartile Range [IQR]: 18) and 35 (56 %) were female. RBC alloantibodies were found in 23 transfused patients (36.5 %) and were predominantly directed against Rh and Kell antigens: Anti-E (65 %), Anti-K (39 %) and Anti-c (22 %) were most common. Excluding an outlier who received 611 RBC units during the study period, the mean number of RBC units transfused per HHT patient at SMH was 22.1 units (Standard Deviation: 40.9, IQR: 17). Six (9.5 %) transfused patients experienced at least one transfusion reaction. ConclusionRBC alloimmunization rate was 36.5 % in our cohort of transfused HHT patients; this is much higher than described in the general population and another transfused HHT cohort. The most commonly observed alloantibodies were Rh and Kell, supporting our policy of prophylactic phenotypic matching for these antigens for all transfused patients with HHT.

Sensory-Motor Neuropathy in Mfn2 T105M Knock-in Mice and Its Reversal by a Novel Piperine-Derived Mitofusin Activator.

Mitochondrial dysfunction is a hallmark of many genetic neurodegenerative diseases, but therapeutic options to reverse mitochondrial dysfunction are limited. While recent studies support the possibility of improving mitochondrial fusion/fission dynamics and motility to correct mitochondrial dysfunction and resulting neurodegeneration in Charcot-Marie-Tooth disease (CMT) and other neuropathies, the clinical utility of reported compounds and relevance of preclinical models are uncertain. Here, we describe motor and sensory neuron dysfunction characteristic of clinical CMT type 2 A in a CRISPR/Casp-engineered Mfn2 Thr105Met (T105M) mutant knock-in mouse. We further demonstrate that daily oral treatment with a novel mitofusin activator derived from the natural product piperine can reverse these neurologic phenotypes. Piperine derivative 8015 promoted mitochondrial fusion and motility in Mfn2-deficient cells in a mitofusin-dependent manner and reversed mitochondrial dysfunction in cultured fibroblasts and reprogrammed motor neurons from a human CMT2A patient carrying the MFN2 T105M mutation. Like previous mitofusin activators, 8015 exhibited stereospecific functionality, but the more active stereoisomer, 8015-P2, is unique in that it has subnanomolar potency and undergoes entero-hepatic recirculation which extends its in vivo half-life. Daily administration of 8015-P2 to Mfn2 T105M knock-in mice for 6 weeks normalized neuromuscular and sensory dysfunction and corrected histological/ultrastructural neurodegeneration and neurogenic myoatrophy. These studies describe a more clinically relevant mouse model of CMT2A and an improved mitofusin activator derived from piperine. We posit that 8015-P2 and other piperine derivatives may benefit CMT2A or other neurodegenerative conditions wherein mitochondrial dysdynamism plays a contributory role. SIGNIFICANCE STATEMENT: Mitochondrial dysfunction is widespread and broadly contributory in neurodegeneration, but difficult to target therapeutically. Here, we describe 8015-P2, a new small molecule mitofusin activator with ∼10-fold greater potency and improved in vivo pharmacokinetics versus comparators, and demonstrate its rapid reversal of sensory and motor neuron dysfunction in an Mfn2 T105M knock-in mouse model of Charcot-Marie-Tooth disease type 2 A. These findings further support the therapeutic approach of targeting mitochondrial dysdynamism in neurodegeneration.

Juvenile Hemochromatosis Connecting Cardiac Arrest and Hypogonadotropic Hypogonadism in a Young Woman

Abstract Juvenile hemochromatosis (JH) is a subtype of hereditary hemochromatosis, a genetic disorder characterized by excessive iron absorption and deposition in various organs, leading to cardiomyopathy, cirrhosis, and diabetes. Endocrine dysfunction is a common manifestation and may appear years before end-organ damage. This report describes a rare case of JH, emphasizing the consequences of delayed diagnosis. A 28-year-old woman with a history of hypogonadotropic hypogonadism presented with cardiac arrest complicated by acute renal failure and cerebral vascular accidents. She initially exhibited signs of severe cardiomyopathy and multiorgan failure, which led to workup for an underlying cause. Laboratory values showed significantly elevated ferritin and transferrin saturation. Subsequent genetic screening revealed HJV gene pathogenic variants consistent with juvenile hemochromatosis. Treatment involved aggressive iron chelation therapy and outpatient referral for cardiac transplant. This case calls for heightened awareness and early screening of JH, particularly among patients with unexplained endocrine dysfunction. Early diagnosis and treatment are paramount in preventing irreversible organ damage and improving patient outcomes.

Real-world experience of emicizumab prophylaxis in Korean children with severe hemophilia A without inhibitors

PurposeHemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors.MethodsThis study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared.ResultsEach of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment.ConclusionThese first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

When Epilepsy Takes Center Stage in Tuberous Sclerosis Complex: A Case Report from the Dermatology Hospital of Bamako

Tuberous Sclerosis Complex (TSC) is a multi-organ genetic disorder characterized by numerous hamartomas found in several organs, including the brain, heart, skin, eyes, kidneys, lungs, and liver. The responsible genes are TSC1 and TSC2, encoding hamartin and tuberin, respectively. The hamartin-tuberin complex inhibits the mammalian target of rapamycin pathway, which controls cell growth and proliferation. Variations in the distribution, number, size, and location of lesions lead to variations in the clinical syndrome, even among family members. Most features of Tuberous Sclerosis Complex become evident only in childhood, after the age of 3, limiting their usefulness for early diagnosis. Identifying patients at risk of severe manifestations is crucial. We report a case of Tuberous Sclerosis Complex inaugurated by epilepsy. It is a 10-year-old girl, a student, who came for consultation for a black spot on her left cheek evolving continuously for seven years. Two months later, this spot, asymptomatic solid lesions appeared on her face, gradually increasing in size and number. In her medical history, she has had convulsive seizures since the age of three, occurring at least five times a year, confirmed by an electroencephalogram. There is an oblong-shaped skin plaque measuring approximately 7x3 cm, erythematous, on the left cheek. Additionally, there are multiple normochromic angiofibromas affecting the nasal pyramid, nasolabial folds, and cheeks. The rest of the dermatological examination is unremarkable. The diagnosis of Tuberous Sclerosis Complex was made. In the presence or absence of cutaneous lesions, when faced with epilepsy in young children, we must always consider Tuberous Sclerosis Complex before ruling out other causes.

The Current State-or Lack Thereof-of Screening and Prevention for Gynecologic Malignancies for Patients With Lynch Syndrome.

Lynch syndrome (LS) is an autosomal dominant genetic disorder that results in an increased risk of ovarian and endometrial cancers. The aim of this paper was to explore the management of this risk through screening and prevention. Published materials and evidence were explored and summarized. This paper demonstrated that while there has been increased awareness and advances in the identification and diagnosis of patients with LS, recommendations for screening and prevention remain less evidence-based. In decisions of management of patients with LS, a shared decision-making model should be used considering individual patient goals.

Clinical and genetic landscape of optic atrophy in 826 families: insights from 50 nuclear genes.

Hereditary optic neuropathies (HON) are a group of diseases due to genetic defects either in mitochondria or in nuclear genomes. The increasing availability of genetic testing has expanded a broader genetic and phenotypic spectrum of HON than previously recognized. To provide systematic insight into the genetic and phenotypic landscape of HON attributed to 50 nuclear genes, we conducted genetic analysis on part of 4776 index patients with clinical diagnosis of HON following our previous study on 1516 probands with Leber hereditary optic neuropathy (LHON) and mitochondrial DNA variants. Exome sequencing was performed in 473 patients diagnosed with nuclear gene-related HON (nHON) and 353 cases with unsolved LHON. Sequencing and variant interpretation in 50 causative nuclear genes indicated that the diagnostic yield of exome sequencing for nHON was 31.50% (149/473), while it was markedly lower at 1.42% (5/353) for LHON patients without primary mtDNA mutations. The top five implicated genes causing nHON in our in-house cohort, OPA1, WFS1, FDXR, ACO2, and AFG3L2, account for 82.46% of mutations. Although OPA1 was the most prevalent causative gene of nHON in both our cohort (53.25%) and literature review (37.09%), the prevalence of OPA1, WFS1, and FDXR differed significantly between our in-house cohort and the literature review (P-adjusted<0.001). Fundus changes in nHON could be stratified into three categories, the most common is optic atrophy at the examination (78.79%), the rarest is LHON-like optic atrophy (3.64%), and the intermediate is optic atrophy with concurrent retinal degeneration (17.57%), which was an independent risk factor for visual prognosis in nHON. A systematic genotype-phenotype analysis highlighted different genetic contributions for ocular, extraocular neurological, and extraocular non-neurological phenotypes. In addition, systemic variant analysis at the individual gene level suggested a revised interpretation of the pathogenicity of a WFS1 heterozygous truncation variant. This study provides a panoramic summary of both the genetic and phenotypic profiles of HON in real-world studies and literature. The category for nHON fundus phenotypes is built for future studies on molecular mechanisms underlying HON and targeted therapies. In addition to routine ophthalmic examinations, careful examination of the extraocular symptoms and meaningful genetic counseling are warranted for patients with nHON.

Social cognition in adults with neurofibromatosis type 1.

Adult patients with the genetic disease neurofibromatosis type 1 (NF1) frequently report social difficulties. To date, however, only two studies have explored whether these difficulties are caused by social cognition deficits, and these yielded contradictory data. The aim of the present study was to exhaustively assess social cognition abilities (emotion, theory of mind, moral reasoning, and social information processing) in adults with NF1, compared with a control group, and to explore links between social cognition and disease characteristics (mode of inheritance, severity, and visibility). We administered a social cognition battery to 20 adults with NF1 (mean age = 26.5 years, SD = 7.4) and 20 healthy adults matched for sociodemographic variables. Patients scored significantly lower than controls on emotion, theory of mind, moral reasoning, and social information processing tasks. No effects of disease characteristics were found. These results appear to confirm that adults with NF1 have a social cognition weaknesses that could explain, at least in part, their social difficulties, although social abilities are not all impaired to the same extent. Regarding the impact of the disease characteristics, the patient sample seemed slightly insufficient for the power analyses performed. Thus, this exploratory study should form the basis of further research, with the objective of replicating these results with larger and more appropriately matched samples.

Evaluation of a Risk Model for Sepsis Early Prediction in Infants with Epidermolysis Bullosa

Abstract Objective Epidermolysis bullosa (EB) is a severe hereditary condition characterized by fragile skin that can lead to complications, including severe infections such as sepsis. Current research on sepsis in children with EB is limited, and there is a need for specific biomarkers that can aid in early detection and management. Methods This study analyzed blood samples from 92 children diagnosed with EB, 42 of whom developed sepsis. We investigated various inflammatory proteins and clinical parameters as potential biomarkers. Multivariate analysis was used to determine predictors of sepsis occurrence. Results Elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), lactate, and decreased oxygen saturation were significantly associated with sepsis in children with EB. The predictive model displayed an area under the receiver operating characteristic curve of 0.80 in the training set and 0.77 in the validation set, indicating good predictive accuracy. Conclusion Our findings suggest that CRP, IL-6, lactate, and oxygen saturation are reliable predictors of sepsis in children with EB. These biomarkers should be monitored closely to facilitate early diagnosis and improve outcomes in this vulnerable population. The study underscores the need for tailored research and diagnostic strategies for children with EB at risk of sepsis.

Immunological Assessment of Interleukin-6 and 8 in Baghdad Patients with β-thalassemia

A genetic disorder known as β-thalassemia major is characterized by a decreased rate of hemoglobin synthesis, which results in inadequate binding of at least one globin chain. Depending on the exact illness, the actuality of deficiencies may vary. The study's model included participants who were not certain they had β-thalassemia, and a control group of fifty people who did not have the disease. The blood tests were assembled by the Medical city Thalassemia Center. between June 1st and October 31, 2023, to be exact. The purpose of this study was to evaluate the serum immunological marker levels, namely IL-6 and IL-8, in Iraqi patients suffering from β-thalassemia. The Panel has approved the survey design for the postgraduate examinations at the School of Baghdad. Human interleukin-6 (IL-6) and interleukin-8 (IL-8) unions were evaluated using the protein-associated immunosorbent assay (ELISA). The review's findings demonstrated that individuals diagnosed with β-thalassemia had notably elevated blood levels of IL-6 and IL-8, which is relevant information. IL-6 foci measuring 33.90±3.42 pg/ml were seen in β-thalassemia patients, whereas the reference group showed levels of 25.21±2.93 pg/ml. Comparably, the benchmark group's estimated IL-8 level was found to be 76.86±23.11 pg/ml, but the patient gathering revealed a higher IL-8 degree of 217.10±44.26 pg/ml. The results of this investigation demonstrate that individuals with thalassemia exhibit an insusceptible dysregulation characterized by concurrent inflammation and immunosuppression.

Communicatively constructing resilience: Exploring family resilience in the experience of hereditary cancer

AbstractObjectiveThe goal was to explore how families communicate to cope with hereditary cancer conditions and identify factors that may enhance resilience and recommended decision‐making.BackgroundFamilies with Hereditary Breast and Ovarian Cancer syndrome (HBOC), Lynch syndrome (LS), and Li‐Fraumeni syndrome (LFS) have an increased lifetime risk of developing cancer. We use the communication theory of resilience (CTR) to examine how families engage in resilience and make health decisions about hereditary cancer risks over time.MethodWe conducted 42 dyadic interviews with families with HBOC, LS, and LFS. Themes emerged through qualitative analysis for each of the resilience processes outlined by CTR (crafting normalcy, communication networks, identity anchors, alternative logics, and foregrounding productive action while legitimizing negative feelings), illustrating how family members manage stressors associated with hereditary cancer over time.ResultsParticipants described enacting each of the five CTR processes to manage the acute and chronic stressors associated with hereditary cancer. We described themes that emerged within each of the five resilience processes.ConclusionFindings demonstrate the ways in which families managing hereditary cancer risks enact resilience processes and how these processes may have a complex relationship to coping and medical decision‐making.ImplicationsFindings demonstrate areas for intervention to support familial resilience.

Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2.

Neurofibromatosis Type 2 (NF-2) is a dominantly inherited genetic disorder that results from mutations in the tumor suppressor gene, neurofibromin 2 (NF2) gene. Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by an inducible genetic knockout of nf2a/b, the zebrafish homolog of human NF2. Analysis of nf2a and nf2b expression reveals ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displays lower expression levels. Induction of nf2a/b knockout at early stages increases the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggers the development of a spectrum of tumors, including vestibular Schwannomas, spinal Schwannomas, meningiomas, and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.

Immunological Changes and Complement Proteins in Major Thalassemia Patients Proteins Post-Splenectomy

Background: Thalassemia is one of the most prevalent genetic disorders worldwide, with infections being a leading cause of mortality due to compromised immune function. Specific Background: Prior studies suggest that major thalassemia patients are highly susceptible to microbial infections, possibly due to altered immunological profiles, particularly immunoglobulin (IgG, IgM) and complement (C3, C4) levels. Knowledge Gap: However, the specific immunological changes pre- and post-splenectomy in these patients remain underexplored. Aims: This study aims to assess the levels of immunoglobulins (IgG and IgM) and complement proteins (C3 and C4) in major thalassemia patients both before and after splenectomy compared to healthy controls. Results: Our analysis of 50 thalassemia patients (34 males, 16 females) and 30 healthy individuals revealed that thalassemia patients exhibited significantly lower levels of C3 and C4 (88.52±24.49, 21.20±6.66) compared to healthy controls (123.50±19.04, 32.87±9.77). IgG and IgM were elevated in patients (1288.12±467.87, 153.46±51.29) compared to controls (1129.93±295.96, 148.67±50.17). Post-splenectomy, patients showed a significant decline in IgG (1001.56±154.14) and IgM (110.08±25.83) levels, along with further decreases in C3 (83.28±24.13) and C4 (17.48±4.86). Novelty: This study provides novel evidence of the immunological shifts in thalassemia patients post-splenectomy, demonstrating significant reductions in both immunoglobulins and complement proteins, thereby elevating the risk of infection. Implications: These findings highlight the spleen's crucial role in maintaining immune competence and suggest that splenectomy in thalassemia patients requires careful post-operative immune monitoring to mitigate infection risks. Highlights: Splenectomy lowers IgG, IgM, C3, and C4 levels in thalassemia patients. Post-splenectomy patients face higher infection risk due to immune weakening. Highlights spleen's crucial role in immune defense for thalassemia patients. Keywords: Thalassemia, Splenectomy, Immunoglobulins, Complement Proteins, Immune Competence

Identification of SLC35A1 as an essential host factor for the transduction of multi-serotype recombinant adeno-associated virus (AAV) vectors.

rAAV is an essential tool for gene delivery in the treatment of genetic disorders, yet the mechanisms of rAAV transduction remain partially understood. GPR108 is vital for the transduction of most rAAV vectors, but not for rAAV5. We aimed to identify host factors that impact AAV5 transduction akin to GPR108. Using a genome-wide CRISPR/Cas9 screen in 293-F cells, we identified SLC35A1, a Golgi apparatus-localized CMP-sialic acid transporter that transports CMP-sialic acid from cytoplasm into the Golgi apparatus for sialylation, is essential to rAAV transduction. Further studies across various AAV serotypes showed SLC35A1 significantly affects vector nuclear import post-internalization. These results underscore the crucial role of SLC35A1 in intracellular trafficking beyond the initial cell attachment of rAAV.

Exploring Dermatoglyphics as a Potential Indicator of Female Infertility: A Review of Current Evidence and Future Directions

Female infertility remains a complex and multifaceted issue, impacting millions globally and necessitating a nuanced understanding of its various underlying factors. Dermatoglyphics, the study of unique skin ridge patterns on fingers, palms, toes, and soles, has garnered attention for its potential in revealing embryonic development insights and genetic markers. This paper investigates the hypothetical associations between dermatoglyphics patterns and female infertility. The literature review in this study synthesizes existing research exploring the potential correlations between dermatoglyphics and factors influencing female infertility. Studies suggest that certain dermatoglyphics patterns might be linked to genetic disorders affecting fertility, such as Turner syndrome and polycystic ovary syndrome (PCOS). The field lacks comprehensive studies that directly establish a causal relationship between dermatoglyphics patterns and female infertility. While intriguing correlations have been proposed, more rigorous research, employing larger sample sizes and advanced methodologies, is essential to substantiate these connections. Additionally, this study highlights the necessity of a comprehensive strategy for identifying and treating female infertility. Even though dermatologics may provide new information, it should only be considered one aspect of a thorough diagnostic process that also includes genetic testing, imaging studies, physical exams, medical histories, and hormonal assays.

Diagnosing a genetic disease in a donor-conceived child: case report and discussion of the ethical, legal, and practical issues.

We describe the unexpected challenges pediatricians may experience when children conceived with assisted reproduction are diagnosed with a rare genetic condition. A local case series triggered a dialogue between many stakeholders with varied expertise. Indeed, diagnosing a genetic disease in a child conceived by embryo, egg, or sperm donation is becoming more common now that genetic testing and in vitro fertilization (IVF) are readily accessible. However, how and whether to share that information with other stakeholders in the gamete donation process has not been fully explored, and the clinical responsibilities of the treating clinician remain ill-defined. This work centers on a patient with a confirmed diagnosis of X-linked nephrogenic diabetes insipidus. Ultimately, we found the same AVPR2 mutation in two children from two families conceived by egg donation. It led to multigenerational cascade diagnoses in the family of the shared, anonymous egg donor. First, we review current genetic testing practices in gamete donation and third-party reproduction. Then, we provide an overview of relevant genomic, ethical, legal, and psychosocial considerations for sharing relevant genomic information. Finally, and to maximize the best interests of genetic relatives, we discuss how a pediatrician can play a role in the early disclosure of relevant clinical information to all stakeholders in the gamete donation process, starting with the fertility clinic. While these clinical cases are cast in a Canadian context, we submit that its important lessons generally apply to medical systems of nearly all developed countries, broadly defined.

Atulyagotreeya Vivaha: A scientific review and case series on non-consanguineous marriage

Atulya Gotra Vivaha (non-consanguineous marriages), emphasized in Ayurveda and supported by modern genetics, plays a crucial role in reducing the risk of congenital anomalies and genetic disorders. Ancient Ayurvedic texts, such as Acharya Charaka’s Atulyagotreeya Sharira Adhyaya, advocate marrying outside one's Gotra to prevent the inheritance of faulty genes and ensure healthier progeny. Modern science also confirms that consanguineous marriages increase the risk of autosomal recessive disorders like mental retardation and congenital anomalies. Despite these insights, cultural norms, ignorance, and lack of awareness drive individuals, especially in less-educated communities, to practice consanguineous marriages, risking the life and health of future generations. This review highlights the need for awareness and education regarding the risks of such unions. Promoting Atulya Gotra marriages can help reduce the burden of genetic disorders and protect every child's life, which is invaluable to the well-being of society.

Anticancer effect of the oncolytic Newcastle disease virus harboring the PTEN gene on glioblastoma.

Glioblastoma (GBM) is one of the most lethal types of human brain cancer and is characterized by rapid growth, an aggressive nature and a poor prognosis. GBM is highly heterogeneous, and often involves several genetic mutations and abnormalities. Genetic disorders or low expression of phosphatase and tensin homolog (PTEN) are associated with GBM occurrence, progression and poor prognosis of patients with GBM. However, effective delivery of PTEN for expression in GBM cells within the brain remains challenging. The aim of the present study was to develop a therapeutic strategy to restore PTEN expression in GBM cells by utilizing a recombinant Newcastle disease virus (rNDV) vector expressing the human PTEN gene (rNDV-PTEN). Methods included infection of U87-MG cells with rNDV-PTEN, followed by assessments of PTEN expression, and cell proliferation, migration and apoptosis. Additionally, an orthotopic GBM mouse model was used to evaluate the in vivo efficacy of rNDV-PTEN. Infection with recombinant rNDV-PTEN treatment increased PTEN protein expression in the cytoplasm of the U87-MG cells, reduced cell proliferation and migration, and induced apoptosis by inhibiting the AKT/mTOR signaling pathway. In the orthotopic GBM mouse model, rNDV-PTEN significantly reduced tumor size and improved survival rates. Magnetic resonance imaging and in vivo imaging analyses confirmed the targeted delivery and efficacy of rNDV-PTEN. These findings highlight the usefulness of rNDV-PTEN as a promising therapeutic agent for GBM, representing a potential advancement in treatment, especially for patients with PTEN deficiency.

Internet-Based Abnormal Chromosomal Diagnosis During Pregnancy Using a Noninvasive Innovative Approach to Detecting Chromosomal Abnormalities in the Fetus: Scoping Review.

Chromosomal abnormalities are genetic disorders caused by chromosome errors, leading to developmental delays, birth defects, and miscarriages. Currently, invasive procedures such as amniocentesis or chorionic villus sampling are mostly used, which carry a risk of miscarriage. This has led to the need for a noninvasive and innovative approach to detect and prevent chromosomal abnormalities during pregnancy. This review aims to describe and appraise the potential of internet-based abnormal chromosomal preventive measures as a noninvasive approach to detecting and preventing chromosomal abnormalities during pregnancy. A thorough review of existing literature and research on chromosomal abnormalities and noninvasive approaches to prenatal diagnosis and therapy was conducted. Electronic databases such as PubMed, Google Scholar, ScienceDirect, CENTRAL, CINAHL, Embase, OVID MEDLINE, OVID PsycINFO, Scopus, ACM, and IEEE Xplore were searched for relevant studies and articles published in the last 5 years. The keywords used included chromosomal abnormalities, prenatal diagnosis, noninvasive, and internet-based, and diagnosis. The review of literature revealed that internet-based abnormal chromosomal diagnosis is a potential noninvasive approach to detecting and preventing chromosomal abnormalities during pregnancy. This innovative approach involves the use of advanced technology, including high-resolution ultrasound, cell-free DNA testing, and bioinformatics, to analyze fetal DNA from maternal blood samples. It allows early detection of chromosomal abnormalities, enabling timely interventions and treatment to prevent adverse outcomes. Furthermore, with the advancement of technology, internet-based abnormal chromosomal diagnosis has emerged as a safe alternative with benefits including its cost-effectiveness, increased accessibility and convenience, potential for earlier detection and intervention, and ethical considerations. Internet-based abnormal chromosomal diagnosis has the potential to revolutionize prenatal care by offering a safe and noninvasive alternative to invasive procedures. It has the potential to improve the detection of chromosomal abnormalities, leading to better pregnancy outcomes and reduced risk of miscarriage. Further research and development in this field is needed to make this approach more accessible and affordable for pregnant women.