Am J Hum Genet. 2025 Jun 5;112(6):1376-1387. doi: 10.1016/j.ajhg.2025.04.003. Epub 2025 Apr 29.

ABSTRACT

The diagnosis of mitochondrial DNA (mtDNA) diseases remains challenging with next-generation sequencing, where bioinformatic analysis is usually more focused on the nuclear genome. We developed a workflow for the evaluation of mtDNA diseases and applied it in a large European rare disease cohort (Solve-RD). A semi-automated bioinformatic pipeline with MToolBox was used to filter the unsolved Solve-RD cohort for rare mtDNA variants after validating this pipeline on exome datasets of 42 individuals previously diagnosed with mtDNA variants. Variants were filtered based on blood heteroplasmy levels (≥1%) and reported association with disease. Overall, 10,157 exome and genome datasets from 9,923 affected individuals from 9,483 families within Solve-RD met the quality inclusion criteria. 136 mtDNA variants in 135 undiagnosed individuals were prioritized using the filtering approach. A focused MitoPhen-based phenotype similarity scoring method was tested in a separate genetically diagnosed "phenotype test cohort" consisting of nuclear gene and mtDNA diseases using a receiving operator characteristic evaluation. We applied the MitoPhen-based phenotype similarity score of >0.3, which was highly sensitive for detecting mtDNA diseases in the phenotype test cohort, to the filtered cohort of 135 undiagnosed individuals. This aided the prioritization of 34 out of 37 (92%) individuals who received confirmed and likely causative mtDNA disease diagnoses. The phenotypic evaluation was limited by the quality of input data in some individuals. The overall pipeline led to an additional diagnostic yield of 0.4% in a cohort where mitochondrial disease was not initially suspected. This highlights the value of our mtDNA analysis pipeline in diverse datasets.

PMID:40306282 | DOI:10.1016/j.ajhg.2025.04.003

J Genet Couns. 2025 Jun;34(3):e70015. doi: 10.1002/jgc4.70015.

ABSTRACT

In recent years, an increasing number of affected children have been diagnosed through whole-exome sequencing (WES); however, it remains unclear whether the problems faced by the patients' parents during the undiagnosed period were resolved. This exploratory qualitative study aimed to clarify the needs of the parents of children who have been diagnosed with rare genetic diseases and determine the factors that may help provide the environment necessary for the family to understand and accept the symptoms and characteristics associated with the disease and live with their affected child. Semi-structured interviews were conducted with the parents of children (less than 18 years old) who participated in a research project, namely the Initiative on Undiagnosed and Rare Diseases (IRUD), at Kyoto University Hospital between November 2016 and December 2021. A reflective thematic analysis generated three themes: the benefits of diagnosis from the perspective of parents, the challenges to be solved after diagnosis, and the significance and issues of revealing genetic information. The results showed that the diagnoses provided psychological satisfaction for the parents. However, diagnosis of a hereditary and rare disease can lead to social and medical isolation, and it was necessary to improve the environment around the affected children's families, mainly by taking advantage of the IRUD research system. The analysis indicated the need for psychological support, which can be provided by the clinical genetic department, the need for a follow-up system in collaboration with various clinical departments, and the need to improve the general public's understanding of human genetics.

PMID:40305385 | DOI:10.1002/jgc4.70015

Sci Rep. 2025 Apr 29;15(1):15093. doi: 10.1038/s41598-025-99539-y.

ABSTRACT

Computational methods for identifying gene-disease associations can use both genomic and phenotypic information to prioritize genes and variants that may be associated with genetic diseases. Phenotype-based methods commonly rely on comparing phenotypes observed in a patient with databases of genotype-to-phenotype associations using measures of semantic similarity. They are constrained by the quality and completeness of these resources as well as the quality and completeness of patient phenotype annotation. Genotype-to-phenotype associations used by these methods are largely derived from the literature and coded using phenotype ontologies. Large Language Models (LLMs) have been trained on large amounts of text and data and have shown their potential to answer complex questions across multiple domains. Here, we evaluate the effectiveness of LLMs in prioritizing disease-associated genes compared to existing bioinformatics methods. We show that LLMs can prioritize disease-associated genes as well, or better than, dedicated bioinformatics methods relying on pre-defined phenotype similarity, when gene sets range from 5 to 100 candidates. We apply our approach to a cohort of undiagnosed patients with rare diseases and show that LLMs can be used to provide diagnostic support that helps in identifying plausible candidate genes. Our results show that LLMs may offer an alternative to traditional bioinformatics methods to prioritize disease-associated genes based on disease phenotypes. They may, therefore, potentially enhance diagnostic accuracy and simplify the process for rare genetic diseases.

PMID:40301638 | DOI:10.1038/s41598-025-99539-y

J Manag Care Spec Pharm. 2025 May;31(5):491-498. doi: 10.18553/jmcp.2025.31.5.491.

ABSTRACT

BACKGROUND: More than 10,000 rare diseases affect more than 30 million Americans, nearly 70% of which manifest in childhood. The drug development pipeline boasts hundreds of candidates for pediatric-onset rare disease, but little is known about the impact of potential approvals.

OBJECTIVE: To quantify US projected product approvals, patients treated, and product revenues for pediatric-onset rare disease treatments through 2033.

METHODS: Four-stage model consisting of a Markov Chain Monte Carlo simulation of US Food and Drug Administration approvals, calculation of eligible patients per clinical trial criteria, and projection of adoption and list price revenues, all using publicly available data.

RESULTS: By 2033 the pipeline will yield approximately 45 new product approvals, a 14% growth in annual treated patients, and an incremental $10.7B in list price drug revenues ($28.2B: 2023; $38.9B: 2033) prior to any health care cost offsets, caregiving impacts, long-term social benefits, or other benefits from treating the additional patients.

CONCLUSIONS: The projected approvals over the next decade will undoubtedly be transformational for the patient communities impacted, many of whom have no currently approved treatments. However, the number of newly identified rare diseases is likely to outpace the rate of new therapies to treat them. Resources are needed to accelerate progress as 95% of pediatric-onset rare diseases are projected to still have no approved treatments in the next decade, and even for the 5% that have some options, more is needed.

PMID:40298308 | DOI:10.18553/jmcp.2025.31.5.491

Psychiatry Res. 2025 Jul;349:116509. doi: 10.1016/j.psychres.2025.116509. Epub 2025 Apr 19.

ABSTRACT

People presenting to centres for rare diseases (CRD) for diagnostic work-up often suffer from mental disorders. The prevalence and distribution of these mental disorders and their relevance for care remain largely unclear and well-controlled multicentre studies are missing. The ZSE-DUO study was a multicentre, prospective, controlled cohort study involving 11 German CRD. In total, 662 adult patients with an unclear diagnosis were evaluated by an additional mental health specialist along with their usual CRD care. Mental disorders were assessed through a standardized clinical examination, including the Mini-DIPS interview. Prevalence of diagnosed mental disorders (ICD-10 coding) was assessed and compared to population prevalence. A total of 54.5 % (361 patients) of adults with unexplained symptoms presenting to a CRD had current mental disorders. Mental disorders were deemed the sole explanation for the entire symptomatology in 53.5 % of cases. In 36.2 % of cases, a combination of a mental disorder with a somatic disease was considered to explain the unexplained symptoms. In 8.3 % of cases, it was assessed that the mental disorder was not involved in explaining the unexplained symptoms. Assessing whether a mental disorder contributes to the patient's symptom complex is crucial for determining suitable treatment strategies in terms of a bio-psycho-social approach.

PMID:40286780 | DOI:10.1016/j.psychres.2025.116509

BMC Med Res Methodol. 2025 Apr 26;25(1):114. doi: 10.1186/s12874-025-02559-5.

ABSTRACT

INTRODUCTION: Rare events data have proven difficult to explain and predict. Standard statistical procedures can sharply underestimate the probability of rare events, such as intravenous immune globulin therapy (IVIg) for bullous pemphigoid.

METHODS: This retrospective cross-sectional study used Department of Defense TRICARE data to determine factors associated with IVIg therapy among bullous pemphigoid patients. We used prior and weighted correction methods for logit regression to solve rare event bias.

RESULTS: We identified 2,720 individuals diagnosed with bullous pemphigoid from 2019 to 2022, of which 14 were treated with IVIg. Patients who received IVIg therapy were younger (65.07 vs. 75.85, P =.0016) and more likely to be female (13 vs. 1, P =.0036). The underestimation with the standard regression model for event probabilities ranged from 11% to 102% using the prior correction method and from 15% to 107% using the weighted correction method.

CONCLUSION: Rare events are low-frequency, high-severity problems that can have significant consequences. Rare diseases and rare therapies are individually unique but collectively contribute to substantial health and social needs. Therefore, correct estimation of the events is the first step toward assessing the burden of rare diseases and the pricing of their therapies.

PMID:40287629 | DOI:10.1186/s12874-025-02559-5

Pharmaceutics. 2025 Mar 31;17(4):450. doi: 10.3390/pharmaceutics17040450.

ABSTRACT

The mRNA- and DNA-based "genetic" COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on the timing and data analysis methods used. Focusing only on lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces the evolution of statistical conclusions on the prevalence of AEs and incidents associated with these vaccines, from initial underestimation of atypical, severe toxicities to recent claims suggesting the possible contribution of COVID-19 vaccinations to the excess deaths observed in many countries over the past few years. Among hundreds of different AEs listed in Pfizer's pharmacovigilance survey, the present analysis categorizes the main symptoms according to organ systems, with nearly all of them being affected. Using data from the US Vaccine Adverse Event Reporting System and a global vaccination dataset, a comparison of the prevalence and incidence rates of AEs induced by genetic versus flu vaccines revealed an average 26-fold increase in AEs with the use of genetic vaccines. The difference is especially pronounced in the case of severe 'Brighton-listed' AEs, which are also observed in COVID-19 and post-COVID conditions. Among these, the increases in incidence rates relative to flu vaccines, given as x-fold rises, were 1152x, 455x, 226x, 218x, 162x, 152x, and 131x for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, and hypertension, respectively. The review delineates the concept that genetic vaccines can be regarded as prophylactic immuno-gene therapies and that the observed chronic disabling AEs might be categorized as iatrogenic orphan diseases. It also examines the unique vaccine characteristics that could be causally related to abnormal immune responses which potentially lead to adverse events and complications. These new insights may contribute to improving the safety of this platform technology and assessing the risk/benefit balance of various products.

PMID:40284445 | DOI:10.3390/pharmaceutics17040450

Int J Tuberc Lung Dis. 2025 May 25;29(5):199-201. doi: 10.5588/ijtld.25.0157.

ABSTRACT

Until relatively recently, bronchiectasis (not due to cystic fibrosis) was considered an orphan disease, lacking clinical and commercial interest, and was rarely diagnosed. Since the 2000s, several working groups have emerged in Europe and the US - with the first register for bronchiectasis launching in Spain - and these have demonstrated the impact bronchiectasis has on health. Today, bronchiectasis is considered the third most common chronic inflammatory disease of the airways, after COPD and asthma, and represents a significant economic burden. We make the case for further characterization of these registries to better understand the heterogeneous epidemiology of bronchiectasis.

PMID:40281677 | DOI:10.5588/ijtld.25.0157

Trends Cardiovasc Med. 2025 Apr 23:S1050-1738(25)00052-0. doi: 10.1016/j.tcm.2025.04.003. Online ahead of print.

NO ABSTRACT

PMID:40280353 | DOI:10.1016/j.tcm.2025.04.003

Nucleic Acids Res. 2025 Apr 22;53(8):gkaf346. doi: 10.1093/nar/gkaf346.

ABSTRACT

Developing customized gene-targeting therapies for the millions of individuals affected by ultra-rare diseases globally requires breaking new ground in therapeutic and regulatory innovation. To address this need, the N=1 Collaborative (N1C) was established to unite academia, industry, patients, and regulators, building an open, shared ecosystem for personalized medicines. Initially focusing on antisense oligonucleotides (ASOs) for rare, fatal neurodegenerative conditions, the N1C aims to develop frameworks that can rapidly extend to other treatment modalities and conditions. Progress in the advancement of personalized therapies has also propelled advancements in the nucleic acids field, offering critical insights into dosing, safety, and efficacy. In October 2024, the N1C convened scientific, regulatory, and advocacy leaders in ASO development for an inaugural meeting. This review report examines the current state of the scientific and clinical ecosystems enabling customized genetic therapies and explores the innovation, frameworks, and systems needed to deliver additional individualized medicines safely and at scale.

PMID:40277082 | DOI:10.1093/nar/gkaf346

Inn Med (Heidelb). 2025 May;66(5):533-539. doi: 10.1007/s00108-025-01892-7. Epub 2025 Apr 24.

ABSTRACT

Rare diseases, defined in the European Union as conditions affecting fewer than five per 10,000 inhabitants, often manifest themselves in childhood, but are playing an increasingly important role in internal medicine due to the significantly improved long-term prognosis and a number of diseases that primarily occur in adulthood. Although noteworthy structures already exist nationally and internationally (networks, registers, databases, self-help groups), awareness of these diseases in daily routine and knowledge of the partly divergent care structures must be improved. There are no specific treatments for many of these diseases, but drugs are increasingly being developed-particularly in oncology-that are subject to special orphan drug status.

PMID:40272470 | DOI:10.1007/s00108-025-01892-7

Indian J Ophthalmol. 2025 May 1;73(5):622-636. doi: 10.4103/IJO.IJO_1542_24. Epub 2025 Apr 24.

ABSTRACT

Rare pediatric retinal disorders present significant challenges in diagnosis and management due to their limited prevalence and diverse clinical manifestations. This paper provides a comprehensive review of select rare retinal disorders affecting the pediatric population, focussing a brief on their epidemiology, clinical characteristics, diagnostic modalities, and therapeutic interventions. Through a systematic examination of current literature and clinical case studies, this review aims to elucidate the distinct features and challenges associated with each disorder. Despite the rarity of these conditions, their impact on visual function and quality of life necessitates heightened awareness among clinicians and researchers to facilitate timely diagnosis, appropriate management, and improved outcomes for affected children as their visual systems are still developing. Furthermore, advancements in diagnostic modalities such as fundus fluorescein angiography, optical coherence tomography, electroretinography, and genetic testing are examined for their role in enhancing our understanding of rare pediatric retinal disorders and facilitating early intervention strategies. The literature selection for this article was conducted through PubMed, Google Scholar, and the Cochrane Library databases. A thorough systematic search was carried out for the concerned diseases. Relevant review articles, original research studies, case series, and reports were examined. Additionally, references from these sources were reviewed and included if they provided pertinent information on the topic. The search was not restricted by publication date.

PMID:40272290 | DOI:10.4103/IJO.IJO_1542_24

Orphanet J Rare Dis. 2025 Apr 23;20(1):193. doi: 10.1186/s13023-025-03691-7.

ABSTRACT

BACKGROUND: The socioeconomic impact of rare diseases has been mostly studied at the macrolevel, but evidence at the microlevel is lacking, which overshadows health-related social inequalities affecting people with rare diseases, namely, health selection effects.

AIM: This study presents an overview of employment and work ability in individuals living with rare diseases, two factors related to health selection effects.

METHODS: A systematic literature review was conducted using the PRISMA checklist. Three electronic databases, PubMed, Embase, and Web of Science, were searched from 2013 to 2023. Eligible studies needed to investigate at least one work-related outcome measuring employment or work ability in individuals living with rare diseases and to compare it with a control group. Indeed, including only studies with matched or standardized control groups is essential for ensuring the reliability and validity of research findings.

RESULTS: Of the 7,694 abstracts identified, 44 studies, including 34 rare diseases, met the inclusion criteria. Administrative databases were used to collect work-related data in 48% of the studies, and 73% of the studies employed matching methods for comparison. Overall, 52% of the studies focused solely on employment, 14% focused solely on work ability and 34% included both categories. Individuals with rare diseases were less likely to be employed or more likely to be unemployed than controls in 68% of the studies and 87% of the studies reported that individuals with rare diseases were more likely to be work disabled. Regarding work ability, 90% of the studies reported more missed work time in cases than in controls, and more perceived impairment at work was found in 100% of the studies.

DISCUSSION/CONCLUSION: These results show that individuals with rare diseases tend to have poor work outcomes, but methodological limitations hamper the understanding of health selection effects. Implications for future research and policy-making are discussed.

PMID:40270029 | DOI:10.1186/s13023-025-03691-7

Sci Transl Med. 2025 Apr 23;17(795):eadn5772. doi: 10.1126/scitranslmed.adn5772. Epub 2025 Apr 23.

ABSTRACT

Calciphylaxis is an orphan disease characterized by dermal microvessel thrombosis, inflicting painful cutaneous necrosis. It occurs predominantly in patients with end-stage kidney disease and has high mortality, elusive pathogenesis, and no approved therapies. We demonstrate that sera from patients with calciphylaxis induced de novo synthesis of interleukin-6 (IL-6) and soluble IL-6 receptor (IL-6R) and stimulated Janus kinase-2 (JAK) and signal transducer and activator of transcription (STAT)-3 phosphorylation in primary human dermal microvascular endothelial cells (ECs). Calciphylaxis skin demonstrated an altered microenvironment characterized by a gain of proximal and distal IL-6 ligand-receptor interactions. Microvessels are the predominant senders and recipients of IL-6 signaling, which, along with up-regulated A disintegrin and metalloproteinase 17 in dermal vasculature and interstitial IL-6R, supported trans-IL-6 signaling in calciphylaxis lesions. Calciphylaxis serum up-regulated thymidine phosphorylase (TYMP) in ECs. TYMP up-regulated IL-6, which activated tissue factor (TF), a primary trigger of the extrinsic coagulation cascade. IL-6-TF signaling in ECs was partially triggered by elevated IL-6 and kynurenine amounts in calciphylaxis serum and was inhibited by anti-IL-6 treatment. The TF-inducing ability of calciphylaxis serum is correlated with disease activity and response to IL-6 inhibitors in ECs. Calciphylaxis is therefore a combination of serum-inducing TYMP-IL-6-TF signaling in ECs and a heterogeneous permissive local dermal microenvironment. The latter is characterized by microvessels initiating IL-6 signaling and multiway cross-talk with adipocytes and eccrine glands, perpetuating the sinister thrombotic milieu. Our results support exploring the IL-6-TF-inducing ability of calciphylaxis serum as an activity marker and IL-6 as a therapeutic target for uremic calciphylaxis.

PMID:40267216 | DOI:10.1126/scitranslmed.adn5772

Med Sci (Basel). 2025 Apr 1;13(2):37. doi: 10.3390/medsci13020037.

ABSTRACT

India's population complexity presents varied challenges in genetic research, and while facilities have gained traction in tier-1 and -2 cities, reliance on international collaborations often delays such investigations. COVID-19 further exacerbated the issues with such sample sharing. Congenital Hyperinsulinism (CHI) is a rare genetic disorder of pancreatic β-cells causing hypoglycaemia in children due to abnormal insulin secretion. Given India's high birth rate and consanguineous populations, annual CHI cases are estimated to be around up to 10,000, with up to 50% having unexplained genetic causes. Diffuse or atypical lesions in such patients often necessitate near-total-pancreatectomy, risking pancreatic exocrine insufficiency and diabetes, requiring lifelong therapy. Also, novel genetic variations complicate accurate diagnosis, risk assessment, and counselling, emphasising the need for rapid genetic assessment to prevent neurological injuries and inform treatment decisions. Despite significant efforts at many institutes, there are no dedicated organisations for CHI in India. With the implementation of the National Policy for Rare Diseases 2021, we plan to form a non-profit organisation, "Congenital Hyperinsulinism India Association (CHIA)", comprising paediatric endocrinologists, paediatricians, geneticists, and independent researchers. The aims of this association are to generate a national database registry of patients, formulate a parent support group and CHIA consortium, design patient information leaflets, as well as foster genomic collaborations and promote clinical trials. Such steps will help sensitise the health authorities and policy makers, urging them to improve the allocation of health budgets for rare diseases, as well as empower patients and their families, contributing towards a better quality of life.

PMID:40265383 | DOI:10.3390/medsci13020037

Clin Transl Sci. 2025 Apr;18(4):e70215. doi: 10.1111/cts.70215.

ABSTRACT

Clinical pharmacologists face unique challenges when developing drugs for rare diseases. These conditions are characterized by small patient populations, diverse disease progression patterns, and a limited understanding of underlying pathophysiology. This tutorial serves as a comprehensive guide, offering practical insights and strategies to navigate its complexities. In this tutorial, we outline global regulatory incentives and resources available to support rare disease research, describe some considerations for designing a clinical development plan for rare diseases, and we highlight the role of biomarkers, real-world data, and modeling and simulations to navigate rare disease challenges. By leveraging these tools and understanding regulatory pathways, clinical pharmacologists can significantly contribute to advancing therapeutic options for rare diseases.

PMID:40261641 | DOI:10.1111/cts.70215

Int J Palliat Nurs. 2025 Apr 2;31(4):181-188. doi: 10.12968/ijpn.2023.0039.

ABSTRACT

BACKGROUND: Low-prevalence diseases (LPDs), previously referred to as orphan diseases or rare diseases, entail a substantial potential for mortality and impose a remarkable burden of symptoms for patients. The process of diagnosing these diseases is often lengthy, and viable treatment options for such conditions are scarce, or in some cases, non-existent.

METHODS: A narrative review was carried out following the Scale for the Assessment of Narrative Review Articles (SANRA) methodology to establish the role of palliative care in the treatment and follow-up of patients with LPDs. A search was carried out by a multidisciplinary team in EMBASE, PUBMED, Web of Science, CINHAL and OVID. Peer-reviewed articles reporting on the role of palliative care in the multidisciplinary treatment of LPDs were included.

RESULTS: The review identified significant areas where palliative care specialists play a crucial role in caring for LPDs. These areas include addressing complex physical and emotional symptoms, assisting patients in adjusting their expectations through genetic counselling, facilitating decision-making across short, medium and long-term perspectives based on disease prognosis, and offering support with care transitions, advanced planning and the grieving process for families.

CONCLUSION: Patients with LPDs and their caregivers experience complex care needs that should be assessed by a palliative care specialist and supported by a multidisciplinary medical group.

PMID:40257763 | DOI:10.12968/ijpn.2023.0039

Eur J Med Genet. 2025 Apr 17;75:105016. doi: 10.1016/j.ejmg.2025.105016. Online ahead of print.

ABSTRACT

A systematic review of case reports, case series, and case-control studies was conducted to quantify the diagnostic delay in 84 rare genetic diseases where neuropsychiatric symptoms may be primary or part of the early clinical presentation. Data abstracted from 1221 published articles encompassing 1838 individual cases revealed a mean diagnostic delay of 9.3 ± 8.7 years, with no significant improvement in time to diagnosis over the 65-year period from 1958 to 2023. Subanalysis of the most recent 10 years, 2014-2023, revealed no change in diagnostic delay, even when stratifying by genetic and other diagnostic tests. Neuropsychiatric symptoms were reported in 68 % of the included cases. Following a definitive diagnosis and optimized management of the underlying rare genetic disease, 66 % of individuals experienced an improvement in their neuropsychiatric symptoms. Despite increasing access to, and substantial advancement in, genetic and other testing, diagnostic delays remain lengthy for individuals affected by these rare genetic diseases. This often results in suboptimal management of the associated neuropsychiatric symptoms. Thus, earlier implementation of genetic testing and other diagnostic tools may reduce these delays, improving patient outcomes and alleviating the burden of diagnostic uncertainty.

PMID:40252994 | DOI:10.1016/j.ejmg.2025.105016

Commun Chem. 2025 Apr 19;8(1):118. doi: 10.1038/s42004-025-01519-w.

NO ABSTRACT

PMID:40253564 | DOI:10.1038/s42004-025-01519-w

Nat Commun. 2025 Apr 18;16(1):3355. doi: 10.1038/s41467-025-58464-4.

ABSTRACT

Therapeutic target identification is challenging in drug discovery, particularly for rare and orphan diseases. Here, we propose a disease signature, TRESOR, which characterizes the functional mechanisms of each disease through genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) data, and develop machine learning methods for predicting inhibitory and activatory therapeutic targets for various diseases from target perturbation signatures (i.e., gene knockdown and overexpression). TRESOR enables highly accurate identification of target candidate proteins that counteract disease-specific transcriptome patterns, and the Bayesian optimization with omics-based disease similarities achieves the performance enhancement for diseases with few or no known targets. We make comprehensive predictions for 284 diseases with 4345 inhibitory target candidates and 151 diseases with 4040 activatory target candidates, and elaborate the promising targets using several independent cohorts. The methods are expected to be useful for understanding disease-disease relationships and identifying therapeutic targets for rare and orphan diseases.

PMID:40251160 | DOI:10.1038/s41467-025-58464-4