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PubMed2025

Innovations in Transgene Integration Analysis: A Comprehensive Review of Enrichment and Sequencing Strategies in Biotechnology.

Understanding the integration of transgene DNA (T-DNA) in transgenic crops, animals, and clinical applications is paramount for ensuring the stability and expression of inserted genes, which directly influence desired traits and therapeutic outcomes. Analyzing T-DNA integration patterns is essential for identifying potential unintended effects and evaluating the safety and environmental implications of genetically modified organisms (GMOs). This knowledge is crucial for regulatory compliance and fostering public trust in biotechnology by demonstrating transparency in genetic modifications. This review highlights recent advancements in T-DNA integration analysis, specifically focusing on targeted DNA enrichment and sequencing strategies. We examine key technologies, such as polymerase chain reaction (PCR)-based methods, hybridization capture, RNA/DNA-guided endonuclease-mediated enrichment, and high-throughput resequencing, emphasizing their contributions to enhancing precision and efficiency in transgene integration analysis. We discuss the principles, applications, and recent developments in these techniques, underscoring their critical role in advancing biotechnological products. Additionally, we address the existing challenges and future directions in the field, offering a comprehensive overview of how innovative DNA-targeted enrichment and sequencing strategies are reshaping biotechnology and genomics.

Transgenes↗

PubMed2024

Identifying transgene insertions in Caenorhabditis elegans genomes with Oxford Nanopore sequencing.

Genetically modified organisms are commonly used in disease research and agriculture but the precise genomic alterations underlying transgenic mutations are often unknown. The position and characteristics of transgenes, including the number of independent insertions, influences the expression of both transgenic and wild-type sequences. We used long-read, Oxford Nanopore Technologies (ONT) to sequence and assemble two transgenic strains of Caenorhabditis elegans commonly used in the research of neurodegenerative diseases: BY250 (pPdat-1::GFP) and UA44 (GFP and human α-synuclein), a model for Parkinson's research. After scaffolding to the reference, the final assembled sequences were ∼102 Mb with N50s of 17.9 Mb and 18.0 Mb, respectively, and L90s of six contiguous sequences, representing chromosome-level assemblies. Each of the assembled sequences contained more than 99.2% of the Nematoda BUSCO genes found in the C. elegans reference and 99.5% of the annotated C. elegans reference protein-coding genes. We identified the locations of the transgene insertions and confirmed that all transgene sequences were inserted in intergenic regions, leaving the organismal gene content intact. The transgenic C. elegans genomes presented here will be a valuable resource for Parkinson's research as well as other neurodegenerative diseases. Our work demonstrates that long-read sequencing is a fast, cost-effective way to assemble genome sequences and characterize mutant lines and strains.

Caenorhabditis elegans↗

PubMed2026

Embryophyte-wide detection of natural Agrobacterium-mediated horizontal gene transfer reveals an ancient role for mini T-DNAs.

Agrobacterium transfers DNA into plant cells, leading to tumors, hairy roots (HR), and natural genetically modified organisms (nGMOs). Transferred DNAs (T-DNAs) from agrobacteria and T-DNA-derived cellular T-DNAs (cT-DNAs) from nGMOs vary considerably and may carry up to 15 different genes. Among these, opine synthase (ops) genes encode the synthesis of opines used as nutrients by the agrobacteria. Earlier studies predicted large numbers of naturally transformed plant species, but only few have been identified and studied so far. We therefore developed a general method to detect cT-DNAs in all publicly available whole genome sequences (WGS) and Sequence Read Archive (SRA) data from land plants. To avoid false positives, we only retained DNA sequences coding for T-DNA proteins. A total of 2614 nGMO species were identified, most are eudicots. However, cT-DNAs were also found in 82 mosses and 75 ferns, showing that Agrobacterium can also generate natural transformants among the early land plants. Analysis of 149 cT-DNA maps revealed different types of T-DNAs. Most notably, these included small T-DNAs (mini T-DNAs) with a single opine synthase gene. Mini T-DNAs are not expected to induce tumors or HRs. The predominance of mini cT-DNAs in mosses and ferns, and the presence of more complex cT-DNAs in spermatophytes, indicate that mini T-DNAs represent the earliest types of T-DNA. Our study also detected unusual T-DNA integration patterns, with multiple copies spread out over several hundreds of kilobases.

DNA, Bacterial↗

PubMed2025

Breeding of yeast strains with intracellular amino acid accumulation for value-added alcoholic beverages.

The yeast Saccharomyces cerevisiae converts amino acids into volatile compounds with fruity and floral aromas during fermentation. These amino acid-derived aroma compounds play a critical role in defining the taste and flavor of alcoholic beverages such as sake, beer, and wine. The productivity of amino acid-derived aroma compounds depends on the intracellular availability of their precursor amino acids. Therefore, breeding yeast strains that accumulate amino acids provides a practical approach to developing alcoholic beverages with more unique and attractive sensory characteristics. In this minireview, we describe the isolation of yeast strains that overproduce branched-chain amino acids and phenylalanine, obtained through conventional mutagenesis of industrial brewing yeasts. We also discuss the mechanisms responsible for the increased production of these amino acids in the mutant strains, including altered feedback regulation and transcriptional control of key enzymes involved in their biosynthesis. In addition, we briefly introduce a plasmid-free genome editing system that enables precise modification of metabolic pathways without the integration of foreign DNA, allowing the construction of strains that are not classified as genetically modified organisms. This method represents a promising tool that allows flexible and fine-tuned engineering of yeast metabolic pathways, including the development of strains with tailored aroma profiles.

Saccharomyces cerevisiae↗

PubMed2026

Genetically Modified and Gene-Edited Organisms-Objectives, Public Perception and Applications.

Genetic modification and genome editing have become important tools in agriculture, animal production, biotechnology, and human medicine, but their safety and societal acceptance remain subjects of debate. This review examines genetically modified (GM) and gene-edited organisms, distinguishing transgenesis from precision genome editing technologies, including CRISPR/Cas9, base editing, and prime editing. Representative applications in crops, livestock, pharmaceutical production, and xenotransplantation are discussed, together with their regulatory framework and public perception. Current scientific assessments indicate that approved GM foods are not inherently more hazardous to human health than their conventional counterparts when evaluated case by case. Potential benefits include improved nutritional quality, biofortification, disease resistance, increased agricultural efficiency, production of therapeutic proteins, and applications in animal health and medicine. Possible concerns include allergenicity, toxicity, unintended genetic or phenotypic effects, altered nutritional composition, environmental consequences, animal welfare issues, and uncertainties associated with long-term or large-scale deployment. Public acceptance varies substantially according to geographical region, application, cultural and ethical considerations, regulatory environment, scientific literacy, and institutional trust. Overall, GM and gene-edited organisms should not be considered a homogeneous category. Their benefits, risks, and societal acceptability depend on the specific organism, genetic modification, intended trait, and context of use, supporting a balanced, evidence-based, and case-specific approach.

acceptance↗

PubMed2026

Hypoimmune platforms: from rejection to immune evasion and regulatory implications.

The growing gap between organ demand and clinical availability has renewed interest in immune-evasive graft strategies, yet rejection and lifelong immunosuppression remain major barriers to durable success. Advances in genome editing enable immune-evasive cell platforms designed to avoid immune recognition while replacing missing function in allogeneic settings. This review summarizes current strategies for engineering immune-evasive grafts that simultaneously suppress adaptive and innate immune responses. We discuss how coordinated modulation of antigen presentation and immune checkpoint pathways can protect transplanted allogeneic cells and tissues from T, NK, and macrophage-mediated rejection. We also present the emerging concept of integrating hypoimmune engineering with genetically modified porcine donors, where extensive genome editing has reduced, but not eliminated, xenogeneic immune barriers. Combining donor genome modification with immune-evasive graft design represents a promising conceptual advance toward xenograft survival, though whether full elimination of systemic immunosuppression is achievable remains to be established clinically. We further examine how the regulatory landscape for these products is evolving across major jurisdictions, and how differences in approval pathways, manufacturing standards, and long-term surveillance requirements shape the path to clinical translation. Finally, we outline the safety considerations and remaining limitations in immune evasion that must be addressed to enable clinical implementation.

Graft Rejection↗

PubMed2026

Risk governance of transgenic plants: bridging science, policy, and public trust.

Transgenic plants and genome editing technologies are revolutionizing agriculture through sustainable approaches to food security, pest management, and adaptation to climate change; but their widespread use is hampered by regulatory systems that are fragmented, ethics considerations, and an ongoing lack of trust from the general public. In contrast to other literature that evaluates regulation processes and public acceptance separately, our review paper introduces a new, holistic approach that includes both technical risk assessment from a scientific perspective, and Codex Alimentarius and OECD standards, and the socio-legal and judicial environment of how the national policy decisions are actually made. The paper provides a comparative, historical analysis of the key difference between product- and process-based risk governance in the USA, the EU, and India. Through the use of case studies with global significance like MON810 maize, Bt Brinjal, and the April 2024 Philippine Court of Appeals' order for cease-and-desist of Golden Rice, we discuss the increasing tension between administrative scientific approvals and precautionary judicial orders. We further explore the emerging exemptions to regulation of Site-Directed Nuclease (SDN-1 and SDN-2) genome edited crops which led to India's revolutionary 2025 commercialization of climate-resilient rice crops. Our review ends with a forward-looking approach to biotechnology regulation policy, making an appeal to shift from static historical dichotomies towards flexible risk-proportionate and internationally coordinated regulatory systems. Finally, we show that global success of agricultural biotechnology is not just about safety verification, but rather about establishment of transparent and communicable institutions that can transform scientific risk assessments into legitimate risk management decisions.

Plants, Genetically Modified↗

PubMed2025

Abiotic conditions can modify the penetrance of transgene-based lethality systems for insect population control.

Modern genetic biocontrol techniques for insect pest management, when compared to chemical insecticide spraying, offer high species specificity and reduced environmental impact, and some of these methods require the environmental release of genetically modified (GM) insects. Because organisms exposed to different environments often show variability in phenotype and gene expression, it is likely that GM insects will also experience environmentally mediated variation, potentially compromising pest control efficiency. This study examines the impact of temperature and nutrition on the early embryonic Tet-off conditional lethality system in Drosophila melanogaster. By independently manipulating parental and offspring environments, we assessed how exposure to variable environments influenced the probability of larval hatching and the transcript abundance of the transgenic system. Our findings revealed that: (i) transgene performance distinctly responds to temperature and nutrition; (ii) thermal stress has a greater impact when embryos, rather than parents, are exposed; and (iii) extreme nutritional conditions can markedly reduce the penetrance of transgenic lethality. Although changes in transgene transcript abundance were observed across environments, these changes did not fully explain the phenotypic variation, suggesting that factors downstream of transcription probably drive variation in transgenic lethality.

Animals↗

PubMed1975

O-acetylserine and O-acetylhomoserine sulfhydrylase of yeast; studies with methionine auxotrophs.

The nutritional requirements of three yeast mutants, previously shown to possess low O-acetyl-L-serine (OAS) and O-acetyl-L-homoserine (OAH) sulfhydrylase activities, were reinvestigated. It was thus found that one mutant (strain No. 16), previously identified as a homocysteine auxotroph, is in fact a double mutant requiring both cysteine and OAH. In agreement with the previous assignment, the other two strains (strains No. 13 and 17) were shown to be true cysteine auxotrophs. These results can best be explained by assuming the cystathionine pathway to be the main route of homocysteine synthesis in this organism. It was further found that extracts of the three mutants contain genetically modified OAS-OAH sulfhydrylases with much reduced catalytic activities. Modified sulfhydrylase was partially purified from strain No. 16 by the same procedure as for the wild-type enzyme. Both OAS and OAH sulfhydrylase activities of the mutant enzyme were copurified and behaved identically on polyacrylamide gel electrophoresis. The enzymatic and physicochemical properties of the purified mutant enzyme were shown to be very similar to those of the wild-type enzyme, except that the catalytic activities of the former were only 3-5% of those of the latter, and that the ratio of OAH sulfhydrylase to OAS sulfhydrylase activity was somewhat lower in the former than in the latter.

Cysteine↗

PubMed1975

Attitudes of patients and their relatives to Huntington's disease.

Reaction to medical, social, and genetic implications of Huntington's disease was evaluated by means of a questionnaire mailed to members of a lay organization concerned with this disease in the United States. One thousand and sixty-five of the approximately 2600 members chose to respond. Patients and those at high risk found physical disabilities most disturbing while mental deterioration and personality change were the most disturbing to spouses of patients. The best source of information regarding the disease for 46% was the lay organization itself. Medical specialists or genetic counsellors were cited as the best source of information by 18%. The transmission risk in Huntington's disease was correctly stated to be one-half by 92% of all respondents including 94% of those who indicated the lay organization as best source and 91% of those who indicated medical specialists and genetic ounsellors as best source. If at risk for Huntington's disease, 86% of respondents would modify their family size; desire for limitation was greatest among those affected but lowest among young adults at high risk. If a screening test were available, 23% at high risk might refuse it.

Adolescent↗

PubMed2026

Generation of full-length wild-type and mutated futsch transgenes in Drosophila-efficient Gibson Assembly of ultra-large cDNAs.

Drosophila Futsch is a key microtubule-associated protein (fly homolog of MAP1B) that regulates microtubule organization, synaptic terminal growth, and neuronal development. Functional analysis of futsch has long been limited by the inability to clone and express a full-length futsch transgene, owing to its exceptional size (~16.5 kb) and extensive repetitive sequences. Here, I present an efficient and reproducible method for cloning both wild-type and mutated full-length Drosophila futsch cDNA (16,488 bp) using Gibson Assembly. These resulting cDNAs were used to generate UAS-futsch transgenes. When expressed in neurons, the wild‑type transgenic Futsch associated with microtubule and rescued the synaptic morphological defects observed in futschK68 mutants. This approach substantially reduces the time and complexity compared with traditional cloning techniques. Furthermore, I highlight common pitfalls encountered during the cloning process and provide practical solutions to enhance cloning efficiency. This protocol offers a broadly applicable and cost-effective framework for cloning otherwise intractable large cDNAs from Drosophila and other organisms.

Animals↗

PubMed2026

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines↗

PubMed2024

Editing of SlWRKY29 by CRISPR-activation promotes somatic embryogenesis in Solanum lycopersicum cv. Micro-Tom.

At present, the development of plants with improved traits like superior quality, high yield, or stress resistance, are highly desirable in agriculture. Accelerated crop improvement, however, must capitalize on revolutionary new plant breeding technologies, like genetically modified and gene-edited crops, to heighten food crop traits. Genome editing still faces ineffective methods for the transformation and regeneration of different plant species and must surpass the genotype dependency of the transformation process. Tomato is considered an alternative plant model system to rice and Arabidopsis, and a model organism for fleshy-fruited plants. Furthermore, tomato cultivars like Micro-Tom are excellent models for tomato research due to its short life cycle, small size, and capacity to grow at high density. Therefore, we developed an indirect somatic embryo protocol from cotyledonary tomato explants and used this to generate epigenetically edited tomato plants for the SlWRKY29 gene via CRISPR-activation (CRISPRa). We found that epigenetic reprogramming for SlWRKY29 establishes a transcriptionally permissive chromatin state, as determined by an enrichment of the H3K4me3 mark. A whole transcriptome analysis of CRISPRa-edited pro-embryogenic masses and mature somatic embryos allowed us to characterize the mechanism driving somatic embryo induction in the edited tomato cv. Micro-Tom. Furthermore, we show that enhanced embryo induction and maturation are influenced by the transcriptional effector employed during CRISPRa, as well as by the medium composition and in vitro environmental conditions such as osmotic components, plant growth regulators, and light intensity.

Solanum lycopersicum↗

PubMed1977

Ionic regulation in genetic translation systems.

The polyelectrolyte theory can provide an interpretation of the interdependence of pH, ionic strength, and polyamines one observes in the activity of ribonuclease acting on RNA. According to this theory: (i) A nucleic acid-enzyme complex and the suspending medium may be considered as two phases in equilibrium, even though within limits, the complex is soluble in water. (ii) The enzymatic catalysis is under tight control of the electrostatic potential generated by the system. Consequently, modification in electrostatic potential will induce a concomitant change in activity. (iii) The electrostatic potential can be modified through action on the system of "modulators", either "external" (ionic strength, pH, temperature, etc.) or "internal" (specific ligands, substrates, protein factors, etc.). Similarities between the reaction of ribonuclease (ribonuclease 3'-pyrimidino-oligonucleotidohydrolase; EC 3.1.4.22) and RNA and those observed with highly organized systems catalyzing DNA, RNA, and protein synthesis suggest that the electrostatic potential also provides an important regulatory mechanism in genetic translation. In this view, an essential function of nucleic acids is to provide their enzyme partners with polyanionic microenvironments within which their catalytic activities are controlled by variation in physicochemical parameters, including the proton concentration induced through "modulation" of the local electrostatic potential.

Catalysis↗

PubMed2026

Development of an Efficient Regeneration and Agrobacterium-Mediated Transformation Protocol for Hosta 'Light Star' Using the RUBY Reporter Gene.

Hosta plantaginea is a perennial shade-tolerant herb of the Liliaceae family, with high ornamental and urban greening value. Hosta 'Light Star' is a newly developed ornamental cultivar with yellow-margined leaves and lilac flowers, but no efficient in vitro regeneration or genetic transformation system has been established for this cultivar to date. In this study, we established a highly efficient in vitro regeneration system for Hosta 'Light Star,' and developed an Agrobacterium-mediated genetic transformation protocol using the RUBY visual reporter gene for non-invasive screening of positive transformants. The optimal callus induction medium was MS + 2 mg/L 6-BA + 0.3 mg/L NAA + 0.05 mg/L 2, 4-D, with a callus induction rate of 53.33% for leaf explants (the optimal explant for sterile seedlings). The optimal adventitious bud proliferation medium was MS + 2 mg/L 6-BA + 0.1 mg/L NAA, with a proliferation coefficient of 5.87. The optimal rooting medium was 1/2 MS + 0.5 mg/L NAA + 0.5 mg/L IBA, with a 100% rooting rate. The optimal transplant substrate was perlite:vermiculite = 2:1, with a 100% transplant survival rate after acclimatization. For Agrobacterium-mediated transformation, the optimal infection parameters were as follows: Agrobacterium suspension OD600 = 0.6, infection time of 10 min, and 200 μM acetosyringone; the optimal selection conditions were 300 mg/L cefotaxime for bacteriostasis and 30 mg/L hygromycin for transformant screening. The final stable transformation efficiency was 2.50% (95% CI 1.23-3.77%), with an escape rate of 16.13%. Transgenic plants showed distinct purplish-red coloration in roots, stems, and leaves, with significantly higher betacyanin accumulation than wild-type plants (p < 0.05). Stable integration and expression of the RUBY gene were confirmed by PCR, RT-PCR, and RT-qPCR. This study establishes the first efficient regeneration and Agrobacterium-mediated transformation system for Hosta 'Light Star,' and validates the feasibility of the RUBY reporter gene as a visual marker for Hosta transformation. This system provides a solid technical platform for functional genomic studies, CRISPR/Cas9-mediated gene editing, and molecular breeding of ornamental traits in Hosta.

Transformation, Genetic↗

PubMed2025

Sweeps in Space: Leveraging Geographic Data to Identify Beneficial Alleles in Anopheles gambiae.

As organisms adapt to environmental changes, natural selection modifies the frequency of nonneutral alleles. For beneficial mutations, the outcome of this process may be a selective sweep, in which an allele rapidly increases in frequency and perhaps reaches fixation within a population. Selective sweeps have well-studied effects on patterns of local genetic variation in panmictic populations, but much less is known about the dynamics of sweeps in continuous space. In particular, because limited movement across a landscape leads to unique patterns of population structure, spatial dynamics may influence the trajectory of selected mutations. Here, we use forward-in-time, individual-based simulations in continuous space to study the impact of space on beneficial mutations as they sweep through a population. In particular, we show that selection changes the joint distribution of allele frequency and geographic range occupied by a focal allele and demonstrate that this signal can be used to identify selective sweeps. We then leverage this signal to identify in-progress selective sweeps within the malaria vector Anopheles gambiae, a species under strong selection pressure from vector control measures. By considering space, we identify multiple previously undescribed variants with potential phenotypic consequences, including mutations impacting known IR-associated genes and altering protein structure and properties. Our results demonstrate a novel signal for detecting selection in spatial population genetic data that may have implications for genomic surveillance and understanding geographic patterns of genetic variation.

Animals↗

PubMed2026

Zebrafish as a Model Organism to Study Neurotoxicity: A Potential Tool for Neuroprotective Drug Discovery.

INTRODUCTION: Danio rerio, the zebrafish, serves as an excellent model in neuroprotective drug discovery due to its conserved nervous system organization, neurotransmitter pathways, antioxidant defenses, and genomic similarity to mammals. METHODS: A systematic literature search following PRISMA 2020 guidelines was conducted across Pub- Med, Scopus, Web of Science, and Google Scholar. Studies published between 2020 and 2025 were prioritized, with earlier key papers included for context. The data on larval, adult, and genetically modified zebrafish models were analyzed for neurotoxic effects, focusing on study design, toxicants, and neurobehavioral or molecular outcomes. RESULTS: Neurotoxicants such as chlorpyrifos, bisphenol, triphenyl phosphate, aluminum, ammonium acetate, arsenic, zinc, acrylamide, methylmercury, and tris (1,3-dichloro-2-propyl) phosphate were shown to cross the zebrafish blood-brain barrier. These exposures caused significant behavioral alterations, neurotransmitter imbalances, oxidative stress, and gene or protein expression changes related to brain function. Analysis of the transgenic zebrafish revealed notable alterations in neuronal development and axonal morphology upon exposure to various neurotoxic chemicals. DISCUSSION: Zebrafish display neurotoxic responses with a close resemblance to mammals, supporting their translational value in neurotoxicity and drug discovery studies. However, limitations such as a less complex brain compared to mammals, quick neuronal regeneration, limited tissue access, and difficulties in drug absorption quantification warrant refinements in zebrafish models. CONCLUSION: Zebrafish offer a versatile, cost-effective, and genetically tractable system for neurotoxicity and neuroprotection research. This systematic review highlights their crucial role in neuroprotective drug discovery while emphasizing the need for improved methodological approaches to enhance translational reliability.

Animals↗

PubMed2025

COL4A1 and COL4A2-related disorders: Clinical features, diagnostic guidelines, and management.

PURPOSE: Collagen type 4 alpha 1 (COL4A1) and alpha 2 (COL4A2) chains, encoded by COL4A1 and COL4A2, are essential for basement membrane integrity, contributing to structural stability and cell regulation. Pathogenic variants in these genes cause a spectrum of autosomal dominant and, more rarely, autosomal recessive disorders, which are collectively known as COL4A1/A2-related disorders. These multisystem disorders can include neurologic, ophthalmologic, renal, and other organ system pathology and vary widely in symptoms, complicating diagnosis and management. METHODS: Using a modified eDelphi method, we obtained consensus from international experts across medical subspecialties on the evaluation and management of COL4A1/A2-related disorders, with consensus set at ≥70% agreement. RESULTS: Consensus was achieved on recommendations for evaluating and managing these conditions. CONCLUSION: Genetic testing and counseling are advised for individuals showing symptoms of COL4A1/A2-related disorders and for at-risk relatives. Given the complexity and rarity of these disorders, management requires a multidisciplinary approach informed by current understanding of disease mechanisms. Recommended care includes neurological and ophthalmological imaging and monitoring of cardiovascular and renal function. Ongoing research is critical to uncover genotype-phenotype links and potential modifiers, with clinical research participation encouraged to advance knowledge and treatments.

Humans↗