Genetic disorders

INTRODUCTION: Genetic mutations or inflammatory, degenerative, or neoplastic conditions can trigger amyloidosis. Hereditary gelsolin amyloidosis is a genetic disorder primarily marked by amyloid fibrils composed of misfolded gelsolin fragments. CASE REPORT: We present three sisters with AGel amyloidosis, illustrating its clinical diversity. Patient 1, a 51-year-old, had bilateral ptosis, ocular discomfort, and dry eye syndrome due to cranial nerve involvement. Patient 2, a 53-year-old, experienced progressive bilateral visual impairment...

IMPORTANCE: Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions. OBJECTIVE: To determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women...

Von-Hippel-Lindau (VHL) is a genetic multisystem disorder characterized by visceral cysts and benign and malignant tumors in various organs. Herein, we present the case of a 23-year-old woman with VHL presenting with multiple gastric neuroendocrine neoplasms (gNENs) type 1 in the context of chronic autoimmune gastritis (CAG). Although gNENs are not acknowledged as a typical entity in VHL patients, in the present case, gNENs were composed of neoplastic cells with clear cytoplasm usually seen in tumors related to VHL disease...

BACKGROUND: Sickle cell disease (SCD) is a genetic hematological disorder associated with severe complications, such as vaso-occlusive crises, acute chest syndrome (ACS), and an increased risk of thromboembolic events, including pulmonary embolism (PE). The diagnosis of PE in SCD patients presents challenges due to the overlapping symptoms with other pulmonary conditions. Our previous study revealed that nearly 96% of computed tomography pulmonary angiography (CTPA) scans in SCD patients were negative for PE, highlighting a gap in understanding the significance of CTPA findings when PE is absent...

Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders characterized by clinical, locus, and allele heterogeneity. This study aims to investigate the phenotype and genotype spectrum of GSDs in a cohort of 14 families from Iran using whole-exome sequencing (WES) and variant analysis. WES was performed on 14 patients clinically suspected of GSDs. Variant analysis was performed to identify genetic variants associated with GSDs. A total of 13 variants were identified, including six novel variants, and seven previously reported pathogenic variants in genes such as AGL, G6PC, GAA, PYGL, PYGM, GBE1, SLC37A4, and PHKA2...

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Its etiology may be associated with genetic, environmental, and lifestyle factors. With the advancement of technology, the integration of genomics, transcriptomics, and imaging data related to AD allows simultaneous exploration of molecular information at different levels and their interaction within the organism. This paper proposes a hypergraph-regularized joint deep semi-non-negative matrix factorization (HR-JDSNMF) algorithm to integrate positron emission tomography (PET), single-nucleotide polymorphism (SNP), and gene expression data for AD...

Dementia, an increasingly prevalent neurological disorder with a projected threefold rise globally by 2050, necessitates early detection for effective management. The risk notably increases after age 65. Dementia leads to a progressive decline in cognitive functions, affecting memory, reasoning, and problem-solving abilities. This decline can impact the individual's ability to perform daily tasks and make decisions, underscoring the crucial importance of timely identification. With the advent of technologies like computer vision and deep learning, the prospect of early detection becomes even more promising...

The adult zebrafish (Danio rerio), which is genetically accessible, is being employed as a valuable vertebrate model to study human disorders such as cardiomyopathy. Intraperitoneal (IP) injection is an important method that delivers compounds to the body for either testing therapeutic effects or generating disease models such as doxorubicin-induced cardiomyopathy (DIC). Currently, there are two methods of IP injection. Both methods have limitations when handling toxic compounds such as doxorubicin, which result in side effects manifesting as severe damage to the body shape and fish death...

BACKGROUND: Opioids are widely used in chronic non-cancer pain (CNCP) management. However, they remain controversial due to serious risk of causing opioid use disorder (OUD). Our main aim was to develop a predictive model for future clinical translation that include pharmacogenetic markers. METHODS: An observational study was conducted in 806 pre-screened Spanish CNCP patients, under long-term use of opioids, to compare cases (with OUD, N.=137) with controls (without OUD, N...

In recent years, the incidence of autism spectrum disorder (ASD) has increased, but the etiology and pathogenesis remain unclear. In this narrative review, we review and systematically summarize the methods used to construct animal models to study ASD and the related behavioral studies based on recent literature. Utilization of various ASD animal models can complement research on the etiology, pathogenesis, and core behaviors of ASD, providing information and a foundation for further basic research and clinical treatment of ASD...

INTRODUCTION: Ehlers-Danlos syndromes (EDS) are genetic connective tissue disorders affecting multiple organ systems that frequently result in connective tissue hyperlaxity and early osteoarthritis. Short- and long-term outcomes after primary total hip arthroplasty (THA) in this patient population remain poorly characterised. The primary purpose of this study is to compare postoperative outcomes and survivorship after primary THA in patients with and without EDS. METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for all patients undergoing primary elective THA between September 2009 and December 2020...

PURPOSE: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot-Marie-Tooth disease type 5. CASE REPORT: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma...

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Fabry disease (FD) is an X-linked multiorgan disorder caused by variants in the alpha-galactosidase A gene (GLA). Depending on the variant, disease phenotypes range from benign to life-threatening. More than 1000 GLA variants are known, but a link between genotype and phenotype in FD has not yet been established for all. p.A143T, p.D313Y, and p.S126G are frequent examples of variants of unknown significance (VUS). We have investigated the potential pathogenicity of these VUS combining clinical data with data obtained in human cellular in vitro systems...

BACKGROUND: Why do potentially traumatic events (PTEs) and substance use (SU) so commonly co-occur during adolescence? Causal hypotheses developed from the study of posttraumatic stress disorder (PTSD) and substance use disorder (SUD) among adults have not yet been subject to rigorous theoretical analysis or empirical tests among adolescents with the precursors to these disorders: PTEs and SU. Establishing causality demands accounting for various factors (e.g. genetics, parent education, race/ethnicity) that distinguish youth endorsing PTEs and SU from those who do not, a step often overlooked in previous research...

Gene therapy is a particularly useful treatment for nervous system genetic diseases, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease (HD). Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL. HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed disease...

BACKGROUND: CYP21A2 gene mutations are responsible for more than 95% of Congenital Adrenal Hyperplasia (CAH) disorders with autosomal recessive inheritance. Most of these pathogenic mutations originate from the CYP21A1P , a neighboring pseudogene with 98% homology, due to unequal crossing over or gene conversion events. Mutation identification of the gene could be beneficial for accurate diagnosis and outcome prediction. METHODS: Twelve unrelated patients with CAH diagnosis were recruited for genetic counseling...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment, a loss of cholinergic neurons, and cognitive decline that insidiously progresses to dementia. The pathoetiology of AD is complex, as genetic predisposition, age, inflammation, oxidative stress, and dysregulated proteostasis all contribute to its development and progression. The histological hallmarks of AD are the formation and accumulation of amyloid-β plaques and interfibrillar tau tangles within the central nervous system...

Non-viral gene delivery is a new therapeutic in the treating genetic disorders. The most important challenge in nonviral gene transformation is the immunogenicity of carriers. Nowadays, The immunogenicity of nanocarriers as a deliverer of nucleic acid molecules has received significant attention. In this research, hematite green nanocarriers were prepared in one step with rosemary extract. Synthetic nanocarriers were investigated by using XRD (X-ray diffraction analysis), FESEM-EDX (field emission scanning electron microscopy with energy dispersive X-Ray spectroscopy), HR-TEM (high-resolution transmission electron microscopy), VSM (value stream mapping), TGA- DTG (thermal gravimetric analysis-differential thermal analysis), FT-IR (fourier-transform infrared spectroscopy), BET (brunauer-emmett-teller) and BJH (barrett-joyner-halenda) analyses...

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurodegenerative disorder of childhood. According to the previous reports, it has various primary signs and symptoms. Because of the simple treatment with riboflavin supplementation, it is important to have suspicious to this disease and begin treatment even before genetic test confirm. We report a five-year-old girl with BVVLS that manifest with hearing problems, first. There was obvious improvement in her disease clinical signs with riboflavin supplementation treatment...