bims-curels Biomed News
on Leigh syndrome
Issue of 2026–02–08
eighteen papers selected by
Cure Mito Foundation
  1. Biomarking MELAS with neurofilament light chain and circulating cell free mitochondrial DNA.
  2. Expanding the cognitive spectrum of mitochondrial diseases.
  3. Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.
  4. Leigh Syndrome Complicated by Takotsubo Cardiomyopathy: A Case Report and Literature Review.
  5. Fahr Syndrome, Hypoparathyroidism and Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome.
  6. Clinical and biochemical footprints of primary mitochondrial disorders: proposed nosology.
  7. Identifying the knowledge needs and preferences of parents of children with rare diseases regarding clinical trials: a scoping review protocol.
  8. Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.
  9. Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.
  10. Screening strategy using a filamentous fungus model to repurpose drugs for mitochondrial complex I deficiencies.
  11. Probability of Mitochondrial DNA heteroplasmy in different tissues from European populations.
  12. Bridging gaps in mitochondrial disease diagnosis: the role of advanced biomarker discovery.
  13. Mitochondrial complex I subunit NDUFS4 overexpression drives glioma progression by regulating mitochondrial function and COX5B.
  14. Genetic Testing and Challenges in a level IV Midwestern NICU: Who, What, When, and Then?
  15. Tell you what I'm gonna do for you: Navigating personal literacies and motivation in rare disease research.
  16. Artificial intelligence in healthcare: the duty to inform patients.
  17. Federated learning for heterogeneous electronic health record systems with cost effective participant selection.
  18. Maximizing Access to Cell and Gene Therapy for Patients with Rare Diseases.
  1. Mol Genet Metab. 2026 Jan 27. pii: S1096-7192(26)00036-3. [Epub ahead of print]147(3): 109753
    Biomarking MELAS with neurofilament light chain and circulating cell free mitochondrial DNA.
    Alessandra Maresca, Monica Moresco, Giulia Amore, Chiara La Morgia, Maria Lucia Valentino, Giada Capirossi, Giulia Sacchetti, Valerio Carelli, Christian Vedeler, Laurence A Bindoff, Kristin N Varhaug.
      Mitochondrial diseases are genetic disorders caused either by nuclear or mitochondrial DNA (mtDNA) alterations and characterized by high genetic and phenotypic variability. The common mtDNA m.3243 A > G variant in the MT-TL1 gene leads to clinical manifestations ranging from the classical MELAS (myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome to milder phenotypes such as MIDD (maternally inherited diabetes and deafness) or a spectrum of clinical features of intermediate severity defined as MELAS-Spectrum. The heterogeneous disease course makes the identification of biomarkers for monitoring disease progression challenging, particularly if we consider the occurrence of stroke-like episodes (SLEs), which remain unpredictable events. Here, we assessed two biomarkers, neurofilament light chain (NF-L) and circulating cell free-mtDNA (ccf-mtDNA), in a cross-sectional study in MELAS patients, including both patients in the interictal period and during SLEs, and MELAS-Spectrum patients. Both biomarkers were significantly elevated in MELAS patients during SLEs, compared to the other patients. In addition, we found significant correlation between NF-L and m.3243 A > G blood heteroplasmy in MELAS patients, as well as between NF-L and clinical severity in the whole patients cohort. Despite the limitations derived from the small sample size and the cross-sectional sample collection, our study confirms the value of NF-L and ccf-mtDNA as biomarkers efficiently hallmarking SLEs, highlighting their potential use to monitor the progression of MELAS.
    Keywords:  Blood biomarkers; Cell free mitochondrial DNA; Inflammation; Mitochondrial diseases; Neurodegeneration; Neurofilaments light chain
    DOI:  https://doi.org/10.1016/j.ymgme.2026.109753
  2. Neurol Sci. 2026 Feb 04. 47(3): 228
    Expanding the cognitive spectrum of mitochondrial diseases.
    Anna Rita Giovagnoli, Costanza Lamperti, Ioana Raluca Mihai, Alessia Catania.
      
    Keywords:  Attention; Memory; Mitochondrial disease; Social cognition; Theory of mind
    DOI:  https://doi.org/10.1007/s10072-026-08827-6
  3. Brain. 2026 Feb 02. pii: awag037. [Epub ahead of print]
    Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.
    Marton Szabo, Daniel Lagos, Emily Cross, Jack Collier, Rita Horvath.
      Primary mitochondrial diseases (PMDs) affect ∼1 in 4,300 individuals, yet mitochondrial dysfunction is also a hallmark of common inherited and acquired disorders. While advances in genomics now allow molecular diagnosis in 30-60% of mitochondrial diseases, treatment remains largely supportive, leading to progressive disability and early mortality. Despite progress in gene-modifying approaches, no approved therapies exist for the majority of mitochondrial diseases, and none of the recent trials have met their primary endpoints, underlining the urgent need for innovative therapeutic strategies. Patients with PMDs have very variable phenotypes, further complicated by increased susceptibility to infections, chronic inflammation and metabolic abnormalities. Recently, it has become evident that certain mitochondrial pathologies, including the loss of mitochondrial membrane integrity, impaired mtDNA maintenance, quality control defects, or respiratory chain defects, result in the release of mtDNA into the cytosol. Infections or metabolic changes also trigger the release of mtDNA, leading to the activation of a sterile innate immune response and interferon signalling. Free mtDNA acts as a pathogen-associated molecular pattern (PAMP), activating innate immune pathways such as the cGAS-STING axis, initiating a sterile inflammatory response. This can be followed by the extracellular release of mtDNA to convey the inflammatory response systemically to communicate between cells or across organs. However, it is unclear whether these pathways worsen the disease phenotype (hyperinflammatory reaction) or, in contrast, rescue the symptoms due to upregulation of compensatory pathways. In this review, we summarise recent advances in understanding the mechanism of mtDNA release and how it activates innate immune signalling in PMDs. We also discuss the implications for pathogenesis, clinical phenotypes, and therapeutic development. Defining the role of circulating mitochondrial material as a biomarker or therapeutic target is a critical step for precision medicine approaches in PMDs. These pathways may also have wider implications for common metabolic, inflammatory, and neurodegenerative disorders with mitochondrial dysfunction.
    Keywords:  mitochondria derived vesicles (MDVs); mtDNA; mtDNA release, primary mitochondrial diseases (PMD); pathogen-associated molecular patterns (PAMPs); sterile-inflammation
    DOI:  https://doi.org/10.1093/brain/awag037
  4. Neuro Endocrinol Lett. 2025 Dec 31. 46(8): 417-422
    Leigh Syndrome Complicated by Takotsubo Cardiomyopathy: A Case Report and Literature Review.
    Zhen-Zhen Jin, Xue-Song Wang, Hua-Bing Tang, Yong Lv.
       BACKGROUND: Leigh syndrome (LS) is one of the most common mitochondrial disorders in the pediatric population, primarily affecting infants and children. It presents with diverse clinical manifestations and is often misdiagnosed or underdiagnosed in clinical practice.
    CASE PRESENTATION: In the present investigation, a retrospective analysis was conducted on a pediatric case manifesting symptoms akin to Takotsubo cardiomyopathy (TTC) characterized by an acute onset. The clinical manifestations and radiographic imaging data of the pediatric patient were analyzed. In addition, genetic screening on the patient and her family members was conducted. Based on these findings, the patient was conclusively diagnosed with LS. Subsequently, the relevant literature was reviewed, and the clinical characteristics of this disease were summarized.
    CONCLUSION: There were no prior reports of LS concomitant with TTC. TTC is a severe complication of LS. Early detection and comprehensive treatment are crucial for the successful recovery of patients with TTC. The case examined in this study provides valuable insights into the successful treatment of LS concomitant with TTC.
  5. AACE Endocrinol Diabetes. 2026 Jan-Feb;13(1):13(1): 102-106
    Fahr Syndrome, Hypoparathyroidism and Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome.
    Jing Li, Xiaodi Wang, Yanmei Guo, Wenwen Wang, Shujuan Wu, Jingmin Sun.
       Background/Objective: We describe a 5-year-old boy with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome presenting with epilepsy, refractory hyperlactatemia, and profound hypoparathyroidism accompanied by Fahr syndrome-like brain calcifications. This case expands the known phenotypic spectrum of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome by demonstrating concurrent parathyroid dysfunction and basal ganglia calcifications. The objective of this report is to characterize this unique neuroendocrine presentation and highlight diagnostic considerations for similar cases.
    Case Presentation: A previously healthy 5-year-old boy presented with 2 days of vomiting, diarrhea, and 1 generalized tonic-clonic seizure. Examination revealed lethargy, positive Chvostek sign, and positive Trousseau sign. Laboratory results showed plasma-free calcium 0.98 mmol/L (reference range, 1.15-1.33), lactate 6.0 mmol/L (reference, 0.7-2.1), and parathyroid hormone 6.62 pg/mL (reference, 12-65). Brain imaging demonstrated symmetrical basal ganglia calcifications. Treatment included levetiracetam, calcium and vitamin D supplementation. Genetic testing confirmed mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome with m.3243A>G mutation. Follow-up showed persistent hyperlactatemia (peak 8.4 mmol/L) and worsening hypoparathyroidism (parathyroid hormone <3 pg/mL).
    Discussion: The severity and persistence of parathyroid hormone suppression in this case contrasts with typical mitochondrial disorder presentations. The concurrence of Fahr-type calcifications and profound hypoparathyroidism suggests potential mitochondrial dysfunction in calcium-regulating tissues.
    Conclusion: This case illustrates a severe neuroendocrine phenotype of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome. Unexplained hypoparathyroidism with basal ganglia calcifications should prompt consideration of mitochondrial disorders, even without classic stroke-like episodes.
    Keywords:  Fahr syndrome; MELAS syndrome; hypoparathyroidism; mitochondrial disorders; neuroendocrine disorders; pediatric endocrinology
    DOI:  https://doi.org/10.1016/j.aed.2025.09.007
  6. Mol Genet Metab. 2025 Dec 11. pii: S1096-7192(25)00696-1. [Epub ahead of print]147(3): 109704
    Clinical and biochemical footprints of primary mitochondrial disorders: proposed nosology.
    Martina Messina, Rebecca Ganetzky, Carlos R Ferreira, Nenad Blau, Shamima Rahman.
      Primary mitochondrial diseases (PMD) are a growing number of disorders caused by mitochondrial dysfunction. There is not yet a consensus on the precise definition of PMD. Therefore, this study presents an approach to developing a nosology for standardized, systematic classification of PMD, harmonized with ICIMD and IEMbase. A total of 452 PMD causative genes were included. The classification includes 18 categories: 1) Disorders of amino acid metabolism; 2) Disorders of peptide and amine metabolism; 3) Disorders of carbohydrate metabolism; 4) Disorders of fatty acid and ketone body metabolism; 5) Disorders of energy substrate metabolism; 6) Mitochondrial DNA-related disorders; 7) Nuclear-encoded disorders of oxidative phosphorylation; 8) Disorders of mitochondrial cofactor biosynthesis; 9) Disorders of mitochondrial DNA maintenance and replication; 10) Disorders of mitochondrial gene expression; 11) Other disorders of mitochondrial function; 12) Disorders of metabolite repair/proofreading; 13) Disorders of lipid metabolism; 14) Disorders of nucleobase, nucleotide and nucleic acid metabolism; 15) Disorders of tetrapyrrole metabolism; 16) Disorders of organelle biogenesis, dynamics and interaction; 17) Disorders of vitamin and cofactor metabolism and 18) Neurotransmitter disorders. We also describe the clinical involvement of 22 organs and systems and laboratory features. The most prevalent symptoms (per gene) were neurological (21.1%), ocular (10.3%), muscular (9.0%), gastrointestinal (8.3%), and cardiovascular (7.9%).
    Keywords:  Biomarkers; ICIMD; IEMbase; Inherited metabolic disorders; Signs and symptoms
    DOI:  https://doi.org/10.1016/j.ymgme.2025.109704
  7. Syst Rev. 2026 Feb 05.
    Identifying the knowledge needs and preferences of parents of children with rare diseases regarding clinical trials: a scoping review protocol.
    Annie P Mabbott, Lisa Knisley, Shannon D Scott.
       BACKGROUND: Rare diseases (i.e., incidence of <1/2000) are individually uncommon, but collectively these 10,000 conditions affect an estimated 473 million people globally, and approximately 70% of rare diseases manifest in childhood. Despite this global impact, 90% of rare diseases lack effective treatment. Treatments for rare diseases are often identified through clinical trials. Identifying parents' knowledge needs and preferences regarding pediatric rare disease clinical trials is an important aspect of empowering parents, improving clinical research practices, and potentially improving recruitment to these vital trials. The aim of the scoping review is to determine the extent, range, and characteristics of the evidence on the knowledge needs and preferences of parents regarding pediatric rare disease clinical trials.
    METHODS: A scoping review will be conducted to identify sources of literature on the topic. A systematic search strategy co-developed with a research librarian will be conducted in six databases (Medline, EMBASE, CINAHL, Scopus, Web of Science, and PsycINFO). Gray literature will be searched via Google, Perplexity AI, the ProQuest Dissertations & Theses Global database, and relevant rare disease organizational websites. Abstract and full-text screening will be conducted by two reviewers independently. Studies in English will be included regardless of study design, date of publication, or location of study/publication. Study quality will be appraised using the Mixed Methods Appraisal Tool. Data will be extracted including study characteristics, population, phenomena under investigation, and knowledge needs and preferences identified. Analysis will involve a descriptive numerical summary and qualitative content analysis. Findings will be presented in evidence tables, and patterns, themes, and gaps across the data will be reported using a narrative approach.
    DISCUSSION: This review will provide an overview of the existing literature regarding parents' knowledge needs and preferences about pediatric rare disease clinical trials. The findings of this review will inform future research and the development of knowledge translation resources for parents of children with rare diseases.
    SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered in Open Science Framework (registration: https://doi.org/10.17605/OSF.IO/QXR8G).
    Keywords:  Clinical trials; Information needs; Knowledge needs; Knowledge translation; Parents; Pediatrics; Rare disease; Scoping review
    DOI:  https://doi.org/10.1186/s13643-026-03094-0
  8. Cell Mol Neurobiol. 2026 Feb 04.
    Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.
    Belinda R Fouché, Sibonelo G Khumalo, Werner J H Koopman, Marianne Venter.
      
    Keywords:   Ndufs4 knockout mouse model; Neuroinflammation; Olfactory bulb; RIG-I like signalling; Transcriptomics
    DOI:  https://doi.org/10.1007/s10571-026-01681-2
  9. Invest Ophthalmol Vis Sci. 2026 Feb 02. 67(2): 6
    Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.
    Avital L Okrent Smolar, Rahul Viswanath, Howard M Bomze, Ying Hao, Sandra S Stinnett, Sidney M Gospe.
       Purpose: The Vglut2-Cre;ndufs4loxP/loxP mouse strain with retinal ganglion cell (RGC)-specific mitochondrial complex I dysfunction develops severe RGC degeneration by postnatal day 90 (P90), with accompanying retinal mononuclear phagocyte (MNP) accumulation. We have reported that continuous exposure to hypoxia partially rescues RGC death in these mice, with minimal effect on MNP abundance. We hypothesized that pharmacological depletion of MNPs with the colony-stimulating factor-1 receptor inhibitor pexidartinib would enhance RGC neuroprotection by hypoxia.
    Methods: Iba1+ retinal MNP depletion was assessed in C57Bl/6J mice fed control or pexidartinib-infused chow beginning at P25. Subsequently, Vglut2-Cre;ndufs4loxP/loxP mice and control littermates were raised under normoxia or hypoxia and fed control or pexidartinib chow from P25 to P90. The neuroprotective effect of pexidartinib and hypoxia alone and in combination was assessed by quantifying RGC soma and axon survival in retinal flat mounts and optic nerve cross-sections.
    Results: Pexidartinib completely depleted retinal MNPs within 1 week of treatment. Untreated Vglut2-Cre;ndufs4loxP/loxP mice exhibited the expected approximately 50% reduction of RGC soma and axon survival at P90 (P < 0.0001 for both). Hypoxia or pexidartinib monotherapy each reduced RGC degeneration by more than one-half, whereas their combination resulted in complete RGC neuroprotection (P < 0.01 for all 3 treatments). Normal myelination patterns were restored in mice receiving dual therapy.
    Conclusions: Pexidartinib effectively depletes retinal MNPs and is neuroprotective in the setting of severe RGC mitochondrial dysfunction. This therapeutic effect is additive to that of hypoxia. Combating retinal neuro-inflammation may therefore be a useful adjunct therapy in mitochondrial optic neuropathies like Leber hereditary optic neuropathy (LHON).
    DOI:  https://doi.org/10.1167/iovs.67.2.6
  10. Life Sci. 2026 Feb 03. pii: S0024-3205(26)00059-7. [Epub ahead of print] 124251
    Screening strategy using a filamentous fungus model to repurpose drugs for mitochondrial complex I deficiencies.
    Carole H Sellem, Nolwenn Bounaix, Mathilde Logerais, Aurélie Renaud, Marc Alexandre d'Elia, Jeremy Richard, Claire Almyre, Guillaume Becker, Jordan Rivron, Anaïs Hoarau, Naïg Gueguen, Valérie Desquiret-Dumas, Aurore Inisan, Sophie Belal, Adélie Mellinger, François Godard, Véronique Paquis-Flucklinger, Olivier R Baris, Stéphane Azoulay, Agnès Delahodde, Déborah Tribouillard-Tanvier, Nathalie Bonnefoy, Vincent Procaccio.
       AIM: This study aimed to repurpose FDA-approved drugs for the treatment of mitochondrial complex I diseases.
    MATERIALS AND METHODS: The NUO-51 protein of the filamentous fungus Podospora anserina is the homolog of the human key catalytic subunit of complex I, NDUFV1. By introducing a pathogenic mutation into P. anserina NUO-51 we created a novel model of complex I deficiency targeting the NDUFV1 subunit. The thermosensitive phenotype of the fungal mutant enabled us to screen a library of nearly one thousand FDA-approved molecules. We have implemented various techniques such as growth analysis, oxygen consumption measurements, complex I activity assays and western blotting on Podospora, Caenorhabditis elegans and human on equivalent NDUFV1 mutant models, treated or untreated with the most effective drugs found during the screen.
    KEY FINDINGS: We isolated a series of compounds able to rescue the growth defect of the Podospora nuo-51 mutant, including ligands of serotonin receptors or transporters. Among the selected drugs, alverine citrate (ALV) and dapoxetine hydrochloride (DAP) emerged as the most active drugs. Both drugs enhanced respiration and complex I activity, not only in the Podospora mutant, but also in Caenorhabditis elegans worms deficient for the NDUFV1 ortholog and in fibroblast from patient carrying NDUFV1 mutations.
    SIGNIFICANCE: Together, our work demonstrates the usefulness of Podospora anserina as fungal model for identifying promising therapeutic candidates for complex I diseases, paving the way for future clinical trials.
    Keywords:  Complex I; Disease models; Drug repositioning; Mitochondrial diseases; Oxidative phosphorylation; Serotonin receptor ligands
    DOI:  https://doi.org/10.1016/j.lfs.2026.124251
  11. Mitochondrion. 2026 Feb 04. pii: S1567-7249(26)00007-3. [Epub ahead of print]88 102117
    Probability of Mitochondrial DNA heteroplasmy in different tissues from European populations.
    Daniel R Cuesta-Aguirre, Ana Onieva, M Pilar Aluja, Cristina Santos.
      Mitochondrial DNA (mtDNA) heteroplasmy complicates genetic analyses due to its variability across individuals and tissues. We analyzed over 400 Spanish blood samples and integrated published Massively Parallel Sequencing (MPS) data from ten additional European tissues. Heteroplasmy was tissue-specific, with skeletal muscle, kidney, and liver showing the highest levels, while the intestines, skin, and cerebellum had the lowest. Blood uniquely displayed more heteroplasmies in coding than non-coding regions. Several conserved positions not previously described as hotspots showed high frequencies. These results establish the first comprehensive tissue-specific heteroplasmic profile of the complete mitochondrial genome in a European population, improving the interpretation of mtDNA variation in forensic and biomedical contexts.
    Keywords:  Heteroplasmic profile; Heteroplasmy; Massively Parallel Sequencing (MPS); Mitochondrial DNA (mtDNA); Point heteroplasmy
    DOI:  https://doi.org/10.1016/j.mito.2026.102117
  12. J Mol Med (Berl). 2026 Jan 31. 104(1): 36
    Bridging gaps in mitochondrial disease diagnosis: the role of advanced biomarker discovery.
    Tendai Makwikwi, Maryke Schoonen, Izelle Smuts, Francois H van der Westhuizen.
      
    DOI:  https://doi.org/10.1007/s00109-026-02646-0
  13. NPJ Precis Oncol. 2026 Jan 30.
    Mitochondrial complex I subunit NDUFS4 overexpression drives glioma progression by regulating mitochondrial function and COX5B.
    Jiang Wu, Juan Li, Li Xu, Yuanyuan Liu, Li Jiang.
      The current study explores the expression, functional significance, and underlying mechanisms of the mitochondrial protein NDUFS4 (NADH:ubiquinone oxidoreductase subunit S4) in glioma cells. TCGA shows that elevated NDUFS4 expression is consistently observed in glioma tissues, correlating with advanced tumor grade and diminished patient survival. Single-cell RNA sequencing further localizes this elevated expression primarily to glioma cells, where NDUFS4 co-expressed genes are integral to cellular respiration and mitochondrial ATP synthesis. These findings were corroborated in patient tissues and various primary and established glioma cell types, confirming consistent NDUFS4 overexpression. Genetic silencing (via shRNA) or CRISPR/Cas9-mediated knockout of NDUFS4 impaired mitochondrial function, evidenced by reduced oxygen consumption rate, inhibited mitochondrial complex I activity and ATP production and increased oxidative stress. NDUFS4 depletion also suppressed glioma cell proliferation, migration, and invasion, while promoting apoptosis. This inhibitory effect is specific to malignant cells, sparing non-cancerous astrocytes. Conversely, NDUFS4 overexpression enhanced mitochondrial activity and promoted aggressive malignant phenotypes in primary and immortalized glioma cells. Further multi-omics integration and experimental investigation established COX5B (cytochrome c oxidase subunit 5B) as an important downstream effector of NDUFS4. shRNA-induced silencing of COX5B replicated the outcomes of NDUFS4 depletion in primary glioma cells, and crucially, restoring COX5B in NDUFS4-silenced glioma cells abrogated the anti-glioma effects. In vivo studies demonstrated that NDUFS4 silencing effectively impeded intracranial growth of patient-derived glioma xenografts by compromising mitochondrial function, downregulating COX5B, inhibiting proliferation and inducing apoptosis. Collectively, these comprehensive data underscore NDUFS4's essential role in glioma progression and position it as a promising therapeutic target for this aggressive malignancy.
    DOI:  https://doi.org/10.1038/s41698-026-01281-9
  14. Am J Perinatol. 2026 Jan 30.
    Genetic Testing and Challenges in a level IV Midwestern NICU: Who, What, When, and Then?
    Hannah McBride, Jessica Scott Schwoerer, Erin Rholl, Krishna Acharya.
       OBJECTIVE: To examine genetic testing strategies and their impact on redirection of care and on reducing prognostic uncertainty in the NICU Study design: Retrospective cohort study from 2020-2021 Results: 133 out of 774 (17%) NICU infants received genetic testing, most commonly whole exome sequencing. A genetic diagnosis was achieved in 33% of cases. 70% of infants who received genetic testing were not critically ill. Decisions about redirection of care were associated with presence of critical illness and not by presence of genetic diagnosis. Many rare diagnoses were made through genetic testing in the NICU, but except for certain chromosomal anomalies, these diagnoses had wide variability in reported phenotypic presentations. Conclusions Genetic testing achieves a unifying diagnosis for many NICU patients, yet many of these diagnoses have variable clinical presentations. Redirection of care in the NICU is reliant on clinical illness severity more often than achievement of a genetic diagnosis. Clinicians must provide meaningful interpretation of genetic test results to families and be prepared to confront uncertainty even after pathogenic variants are found.
    DOI:  https://doi.org/10.1055/a-2800-4140
  15. Patient Educ Couns. 2026 Feb 02. pii: S0738-3991(26)00033-9. [Epub ahead of print]146 109500
    Tell you what I'm gonna do for you: Navigating personal literacies and motivation in rare disease research.
    Kara A Ayik.
      
    DOI:  https://doi.org/10.1016/j.pec.2026.109500
  16. Cas Lek Cesk. 2025 ;164(7-8): 324-327
    Artificial intelligence in healthcare: the duty to inform patients.
    Tomáš Doležal, Adam Doležal.
      Artificial intelligence (AI) is increasingly used in healthcare, ranging from diagnostic and therapeutic applications to administrative support. Its implementation raises not only medical and ethical, but also legal challenges. This review article focuses on the healthcare provider's duty to inform patients about the use of AI systems in clinical practice. It examines the ethical dimension of this duty, particularly the principles of autonomy and the patient's right to information and explanation and analyzes the legal framework arising from the EU Artificial Intelligence Act, GDPR, the Council of Europe Framework Convention, and the Czech Health Services Act. The authors conclude that the patient's right to be informed about the use of AI and to understand its role in clinical decision-making can be derived from the concept of informed consent, even though it is not yet explicitly enshrined in law. The article also offers recommendations for clinical practice regarding the scope and depth of information disclosure.
    Keywords:  artificial intelligence; ethics; healthcare; healthcare services; informed consent; patient autonomy; right to explanation
  17. Sci Rep. 2026 Feb 01.
    Federated learning for heterogeneous electronic health record systems with cost effective participant selection.
    Jiyoun Kim, Junu Kim, Kyunghoon Hur, Edward Choi.
      The increasing volume of electronic health records (EHRs) presents the opportunity to improve the accuracy and robustness of models in clinical prediction tasks. Unlike traditional centralized approaches, federated learning enables training on data from multiple institutions while preserving patient privacy and complying with regulatory constraints. In practice, healthcare institutions (i.e., hosts) often need to build predictive models tailored to their specific needs (e.g., creatinine-level prediction, N-day readmission prediction) using federated learning. When building a federated learning model for a single healthcare institution, two key challenges arise: (1) ensuring compatibility across heterogeneous EHR systems, and (2) managing federated learning costs within budget constraints. Specifically, heterogeneity in EHR systems across institutions hinders compatible modeling, while the computational costs of federated learning can exceed practical budget limits for healthcare institutions. To address these challenges, we propose EHRFL, a federated learning framework designed for building a cost-effective, host-specific predictive model using patient EHR data. EHRFL consists of two components: (1) text-based EHR modeling, which facilitates cross-institution compatibility without costly data standardization, and (2) a participant selection strategy based on averaged patient embedding similarity to reduce the number of participants without degrading performance. Our participant selection strategy sharing averaged patient embeddings is differentially private, ensuring patient privacy. Experiments on multiple open-source EHR datasets demonstrate the effectiveness of both components. With our framework, healthcare institutions can build institution-specific predictive models under budgetary constraints with reduced costs and time.
    Keywords:  Electronic Health Records (EHR); Federated Learning (FL)
    DOI:  https://doi.org/10.1038/s41598-026-38299-9
  18. Hum Gene Ther. 2026 Feb 04. 10430342261422716
    Maximizing Access to Cell and Gene Therapy for Patients with Rare Diseases.
    Terence R Flotte, Guangping Gao.
      
    DOI:  https://doi.org/10.1177/10430342261422716
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