bims-tyki2d Biomed News
on Thymidine kinase 2 deficiency
Issue of 2026–01–18
nine papers selected by
Zoya Panahloo, UCB



  1. Nat Biotechnol. 2026 Jan;44(1): 38
      
    DOI:  https://doi.org/10.1038/s41587-025-02973-6
  2. An Pediatr (Engl Ed). 2026 Jan 13. pii: S2341-2879(25)00465-X. [Epub ahead of print] 503995
      Advances in the diagnosis of rare genetic diseases and growing knowledge of the genes that cause them have allowed the exponential development of advanced therapies. Today, there is a therapeutic armamentarium that, while limited, was unthinkable years ago and is constantly evolving. Given the complexity of their mechanisms of action, the feasibility of clinical trials and the authorization by regulatory agencies, advanced therapies need to be investigated for the management and follow-up of pediatric patients. Ongoing pharmacovigilance of these therapies is also necessary to evaluate patient responses and outcomes. At this stage, novel phenotypes of disease emerge that had never been treated before. Prognostic factors and specific indications are also established, underscoring the importance of assessing each patient based on their particular characteristics, in adherence to the principles of the personalized medicine approach. The aim of this article is to provide a comprehensive summary of concepts and strategies as an introduction to the topic of advanced therapies for genetic diseases, taking into account their broad scope and their ongoing evolution and advancement.
    Keywords:  Advanced therapies; Edición génica Terapia RNA; Gene editing; Gene therapy; Protein therapeutics; RNA therapy; Terapia génica; Terapia proteína; Terapias avanzadas
    DOI:  https://doi.org/10.1016/j.anpede.2025.503995
  3. Orphanet J Rare Dis. 2026 Jan 13.
      
    Keywords:  Canadian clinical practice; Conventional genetic tests; Cost analysis; Rare genetic disorders
    DOI:  https://doi.org/10.1186/s13023-025-04182-5
  4. Clin Transl Sci. 2026 Jan;19(1): e70464
      Clinical genomics and pharmacogenomics have largely remained separate fields, though some genetic variants have overlapping disease risk and drug implications. However, the extent of this overlap is not well studied. To explore this gap, we cross-referenced genes from the American College of Medical Genetics Secondary Findings v3.2 list with genomic databases and drug labeling to identify gene-phenotype pairs with overlapping clinical genomics and pharmacogenomic implications. We searched GeneReviews and PharmGKB (now called ClinPGx) for each gene-phenotype pair and reviewed the FDALabel database contraindications or warnings. Targeted therapies for specific germline/somatic variants were excluded. PGx-trained pharmacists and a genetic counselor classified gene-phenotype pairs into three levels: Level 1 (Food and Drug Administration's or guideline-driven recommendations), Level 2 (potential pharmacotherapy implication), and Level 3 (no/weak interactions). Among 97 gene-phenotype pairs reviewed, 22 (23%) were Level 1, 31 (32%) were Level 2, and 44 (45%) were Level 3. Pharmacotherapy implications included risks inferred by disease pathology (e.g., anticoagulants and hereditary hemorrhagic telangiectasia) and less obvious associations (e.g., Marfan syndrome and fluoroquinolones). Unrecognized medication implications may pose patient safety risks. Greater research, information consolidation and dissemination, and multidisciplinary collaboration among clinical genomics specialists, pharmacogenomic specialists, and other practitioners are essential as genetic testing becomes routine in clinical care.
    Keywords:  clinical genomics; contraindications; multidisciplinary care; pharmacogenomics; pharmacy; rare disease; secondary findings
    DOI:  https://doi.org/10.1111/cts.70464
  5. Med J Aust. 2026 Jan;224(1): e70135
      Genomic newborn screening (gNBS) can screen for a broad range of genetic conditions, potentially enabling early treatment and improving health outcomes. However, it remains outside publicly funded programmes due to limited evidence and substantial implementation challenges. Offering gNBS in the interim as a fee-for-service option in Australia risks creating inequitable healthcare access, fragmenting care and limiting control over genomic data. Conversely, prohibiting private access may unfairly deny potential benefits to individual infants and families. This article discusses the ethical and practical implications of offering gNBS on a fee-for-service basis prior to a decision being made regarding public funding. Although fee-for-service gNBS undermines equitable access, regulated private offerings by public genomics services could mitigate some of the risks. We emphasise the need for large-scale, well-designed research studies to inform the development and equitable implementation of robust gNBS programmes within public healthcare frameworks.
    Keywords:  ethics; genetic testing; health equity
    DOI:  https://doi.org/10.5694/mja2.70135
  6. J Genet Couns. 2026 Feb;35(1): e70164
      Sponsored genetic testing is where a non-traditional payer (e.g., pharmaceutical company, patient advocacy group) covers the cost of diagnostic genetic testing for a qualified individual in exchange for patient data. Although previous research has shown the public is hesitant when sharing medical information with for-profit researchers, there has been little research on genetic counselor (GC) attitudes toward sponsored testing. This study used mixed methods to assess GCs' awareness of and attitudes toward sponsored testing and perceived implications on informed consent processes. Board-certified GCs were eligible to complete an online survey. Respondents with experience ordering sponsored testing were invited to participate in a focus group. Descriptive statistics were performed for survey data. Qualitative data were iteratively analyzed using codebook thematic analysis. The survey was completed by 68 GCs, of which 97% were female, 41% had 1-4 years of GC experience, and 75% had experience ordering sponsored testing. 61% (n = 41/67) of survey respondents felt the advantages of sponsored testing outweigh the disadvantages, and that there are additional components of informed consent for sponsored testing compared with standard practice. Of those who completed the survey, 12 participated in one of four focus groups. Most focus group participants felt that the lack of monetary cost and insurance billing were advantages of sponsored testing, as they increased access to testing for their patients. Perceived disadvantages included lack of transparency surrounding data sharing practices and the inability to customize sponsored panels. Many focus group participants felt that additional components of informed consent should be discussed with the patient when ordering sponsored testing, such as secondary use of data and future contact for research contribution. The majority of focus group participants described that when discussing sponsored testing with patients, they offer multiple test options and use shared decision-making to explore patients' perceptions of sponsored testing. Our study suggested that it is important for providers to thoughtfully approach conversations on sponsored testing.
    Keywords:  data sharing; free genetic testing; genetic counseling; informed consent; no‐cost genetic testing; sponsored genetic testing
    DOI:  https://doi.org/10.1002/jgc4.70164
  7. J Clin Transl Sci. 2025 ;9(1): e265
      Research participants should be informed of genetic test results that could impact their health, particularly when they have expressed interest in receiving such information. Furthermore, the return of genetic test results is essential to improve trust, transparency, and health equity. However, investigators often encounter barriers in returning genetic test results to research participants. We examined genomic research at a large, research-intensive medical school and found less than 6% of protocols included plans to return results to participants. This study describes our development of protocols for returning primary and secondary genetic test results and implementation of a Genomic Return of Results (gROR) service. This arose through a collaboration with experts in community engagement, genetics, and pathology to consider consent adequacy, analytical/clinical validity, and clinical utility when returning results. The gROR service reduces investigator burden and provides participants with genetic information and guidance to address any potential health risks. Genetic results are returned by a genetic counselor at no cost to participants or their family. Investigator costs are subsidized to incentivize the delivery of actionable genetic test results to research participants. Our approach prioritizes transparency, accessibility, and informed decision-making, thereby promoting equitable sharing of genetic knowledge and personalized healthcare interventions.
    Keywords:  Return of results; genetics; genomics; research participants; service
    DOI:  https://doi.org/10.1017/cts.2025.10197
  8. NAR Mol Med. 2026 Jan;3(1): ugaf042
      For quite some time, knowledge about mitochondria and the mitochondrial genome has been primarily limited to energy production. However, there is now increasing evidence that they have many important roles in cell function and that synergy between the nuclear and mitochondrial genomes is an essential prerequisite to developmental outcome. This review describes the mitochondrial genome and its contribution to overall cellular genomic content; and discusses mitochondrial DNA (mtDNA) inheritance. mtDNA homoplasmy and heteroplasmy are defined and distinctions between pathogenic and non-pathogenic rearrangements are drawn; how they are transmitted; and their effects on oocyte quality and developmental outcomes. This is followed by analysis of mtDNA replication and changes in mtDNA copy number during development; why they need to happen; and how they influence developmental outcomes. Changes to nuclear DNA methylation events are then discussed in the context of changes to mtDNA replication throughout development. This leads to the concept of 'genomic balance', which defines how cells at any stage of development require adjustments to both genomes to ensure successful cellular function and development; and how this process can be perturbed by some of the more invasive assisted reproductive technologies designed to treat infertility and mtDNA disease.
    DOI:  https://doi.org/10.1093/narmme/ugaf042
  9. Genet Med Open. 2026 ;4 103480
       Purpose: Underutilization of genetic testing among Hispanic males results in higher rates of variants of uncertain significance (VUS). We examined the impact of VUS on decision making and behavioral intentions.
    Methods: We conducted a nationwide survey of 807 US Hispanic males aged ≥40 in English and Spanish on perspectives about genetic testing results. Logistic regression was used to examine predictors of worry and behavior change with a hypothetical VUS result.
    Results: Over half of Hispanic male participants would still participate in genetic testing with a 1 in 5 chance of VUS. However, 36% were at least somewhat likely to regret testing and 49.9% would worry about cancer risk with VUS results. In addition, 56.3% were somewhat or very likely to change behavior due to a VUS, such as getting checked by the doctor more often or telling family members to get checked. Younger age and college education were associated with more worry and intended behavior change.
    Conclusion: Although many Hispanic males are interested in genetic testing despite the higher likelihood of VUS, potential consequences include decisional regret, anxiety, and even changes in behavior. Effective counseling and support are important for minoritized groups undergoing genetic evaluation to avoid the potential to exacerbate health disparities.
    Keywords:  Genetic counseling; Genetic testing; Hispanic; Variants of uncertain significance
    DOI:  https://doi.org/10.1016/j.gimo.2025.103480