bims-tyki2d Biomed News
on Thymidine kinase 2 deficiency
Issue of 2026–02–15
eleven papers selected by
Zoya Panahloo, UCB
  1. Referral route: a determinant of inequity for children with undiagnosed genetic diseases?
  2. The Potential and Challenges of Online Genetic Counseling in Japan.
  3. Rare and resilient: Longer-term experiences of families after genetic evaluation in the neonatal intensive care unit.
  4. Short telomeres in mitochondrial DNA depletion disorders.
  5. Online Genetic Counseling as a Solution for Unmet Needs in Genetic Medicine: The First Survey in Japan.
  6. Elective genomic screening: results of the implementation of a whole genome sequencing program at a medical check-up unit in Spain.
  7. Impact of a digital platform on genetic counselling encounters in the screening context.
  8. A roadmap for a patient-centred approach to Pompe disease management.
  9. Impact of Digital Tools on Knowledge, Genetic Counseling, and Testing Uptake: A Systematic Review and Meta-analysis.
  10. Perspective - The Role of Peripheral Outreach Programs for Genetic Disorders for Optimizing Healthcare.
  11. Genetic Diagnosis and Discovery Enabled by Large Language Models.
  1. Front Genet. 2026 ;17 1692489
    Referral route: a determinant of inequity for children with undiagnosed genetic diseases?
    Zeyu Tang, Emily K Mis, Saquib A Lakhani.
      Individuals with rare genetic diseases collectively comprise 3.5%-5.9% of the population, roughly 400 million people worldwide. Undiagnosed rare disease programs have leveraged next-generation sequencing technologies to facilitate genetic diagnoses, thereby shortening the complex diagnostic odysseys that many of these patients and their families endure. However, enrollment data suggest disparities in access to undiagnosed genetic disease programs among racial and ethnic minorities. To better understand this issue, we conducted a retrospective review of our rare undiagnosed disease program to assess whether referral route was a determinant of disparities for minoritized racial and ethnic communities. Participants enrolled in the Yale Pediatric Genomics Discovery Program from 2016 to 2022 were self-categorized into four racial and ethnic groups: Hispanic/Latinx (any race), non-Hispanic White, non-Hispanic Black/African American, non-Hispanic Other. Route of referral was classified as Inpatient, Outpatient, or Outside/Self referrals. Completion rates were the percentage of participants who completed enrollment compared to their respective group. Demographics for program participants were different from Yale-New Haven Children's Hospital demographics, with over-representation of non-Hispanics Whites. Direct inpatient recruitment had a higher yield of Hispanic individuals, which was offset by under-representation of minoritized individuals in the Outside/Self setting. Inpatients had lower referral completion rates compared to Outpatient and Outside/Self referrals. These data suggest that the route of referral may represent different levels of access to care, and inpatient recruitment may be leveraged to promote participation by some minoritized communities. We encourage other programs to examine their cohorts for representation and identify strategies for improving participation.
    Keywords:  disparities; genomics; race and ethnicity; rare disease; undiagnosed
    DOI:  https://doi.org/10.3389/fgene.2026.1692489
  2. JMA J. 2026 Jan 15. 9(1): 171-172
    The Potential and Challenges of Online Genetic Counseling in Japan.
    Yoshimitsu Fukushima.
      
    Keywords:  Genetic counseling; Genetic counselor; Genomic Medicine Promotion Act; Online genetic counseling
    DOI:  https://doi.org/10.31662/jmaj.2025-0533
  3. Genet Med Open. 2026 ;4 103490
    Rare and resilient: Longer-term experiences of families after genetic evaluation in the neonatal intensive care unit.
    Siwaar Abouhala, Maya C Del Rosario, Ingrid A Holm, Monica H Wojcik.
       Purpose: Many rare genetic conditions manifest soon after birth and result in admission to the Neonatal Intensive Care Unit (NICU), where prior research suggests that parents experience high levels of stress and uncertainty. However, further insight into parent-reported, longer-term outcomes for these infants and their families is needed.
    Methods: We undertook a qualitative analysis of parent-reported experiences with genomic care over the course of their NICU admission and beyond, after an initial quantitative study of 110 families who received genetic evaluation in the NICU, in a mixed-methods approach. Twenty families participated in individual semistructured interviews eliciting the impact of the NICU experience and genetic diagnostic odyssey on the infant and family.
    Results: We identified 4 main themes: (1) Rare Disease as "Culture Shock," (2) Parental Trauma and Stressors, (3) Family Resiliency, and (4) Hospital System Recommendations. Early, rapid, and broad genomic testing was appreciated by parents, although additional genomic- and nongenomic supports after NICU discharge were desired. Stressors in the NICU related to uncertainty and critical illness occurred independent of genetic testing applications or results. Parents reported adapting their expectations regarding the benefits of a genetic diagnosis over time, ultimately focusing on day-to-day care and finding pride in medical and social resilience.
    Conclusion: The NICU experience, particularly for infants with rare conditions, has long-lasting impact on the family. Enhanced attention to longitudinal supports from NICU to home may be beneficial for families undergoing genetic diagnostic odysseys.
    Keywords:  Family experience; Genetic; Genetic diagnosis; Neonatal intensive care unit; Parent support
    DOI:  https://doi.org/10.1016/j.gimo.2025.103490
  4. Mitochondrion. 2026 Feb 10. pii: S1567-7249(26)00021-8. [Epub ahead of print]88 102131
    Short telomeres in mitochondrial DNA depletion disorders.
    Yumi Dille, Emmanouil Rampakakis, Geraldine Aubert, Christelle Dassi, William Mannherz, Saoussen Berrahmoune, Myriam Srour, Daniela Buhas, Suneet Agarwal, Kenneth A Myers.
      Mitochondrial DNA (mtDNA) depletion disorders (MDDs) are rare, genetically diverse conditions marked by a significant reduction in mtDNA, primarily affecting energy-demanding tissues such as muscle, liver, and brain, sometimes leading to catastrophic multisystem failure. In a cohort of patients with MDDs, we measured telomere length in lymphocytes, granulocytes, T cells, and B cells, and compared to healthy controls. Telomere length was shorter overall in patients with MDDs, with the most significant differences observed in granulocytes. The observation that mtDNA depletion is associated with shorter telomeres may provide insight into MDD pathophysiology. Telomere length may have potential as a biomarker in mitochondrial disease, but further study is needed.
    Keywords:  C10orf2; DGUOK; Mitochondrial DNA depletion disorders; POLG; RRM2B; SUCLA2; SUCLG1; TK2; TYMP; Telomere length; Telomeres
    DOI:  https://doi.org/10.1016/j.mito.2026.102131
  5. JMA J. 2026 Jan 15. 9(1): 160-170
    Online Genetic Counseling as a Solution for Unmet Needs in Genetic Medicine: The First Survey in Japan.
    Haruka Murakami, Satomi Inoue, Kaoru Fujinami, Tatsuo Matsunaga, Kazuki Yamazawa.
       Introduction: The demand for genetic counseling is increasing in Japan owing to rapid advancements in genetic medicine and increased utilization of genetic testing. However, access to genetic counseling remains limited, particularly in rural areas, owing to a shortage of certified professionals. Online genetic counseling (OGC), a form of telemedicine, offers a potential solution to address these disparities. Although OGC is widely practiced in Western countries, its implementation and systemic evaluation in Japan remain limited. To our knowledge, this study represents the first attempt in Japan to systematically assess the effectiveness, challenges, and user satisfaction of OGC compared with in-person genetic counseling (IPGC) in the context of the Japanese health care system.
    Methods: This cross-sectional, single-center study involved 49 participants (15 OGC, 34 IPGC) who received genetic counseling at the NHO Tokyo Medical Center between July 2020 and January 2025. Participants completed anonymous questionnaires assessing demographic characteristics, satisfaction with counseling, and perceived advantages and disadvantages. Statistical analyses included Mann-Whitney U tests, chi-square tests, and Fisher's exact tests. Free-text responses were analyzed using conventional content analysis and word cloud visualization.
    Results: Overall satisfaction was high in both groups, with all participants selecting "Strongly agree" or "Agree" regarding satisfaction. However, the IPGC group scored significantly higher in counselor introduction, responsiveness, and overall satisfaction. OGC participants had significantly longer travel times and were more likely to be in their 20s-30s. Key advantages of OGC included convenience and accessibility, whereas disadvantages included concerns about privacy and technical issues.
    Conclusions: OGC has high potential to improve access to genetic services in Japan, particularly for individuals in remote areas. Despite high satisfaction, challenges such as communication limitations, privacy concerns, and lack of insurance coverage must be addressed. Policy reforms, improved infrastructure, and further large-scale studies are needed to support the widespread implementation of OGC in Japan.
    Keywords:  clinical genetics; genetic counseling; health care accessibility; online genetic counseling (OGC); patient satisfaction; telemedicine
    DOI:  https://doi.org/10.31662/jmaj.2025-0157
  6. Front Genet. 2025 ;16 1722462
    Elective genomic screening: results of the implementation of a whole genome sequencing program at a medical check-up unit in Spain.
    Bibiana Palao, Miriam Leon-Otegui, Raquel Bernad, Maria Moreno-Coca, Elena Ordoñez, Elena Góngora, Isabel Castilla, Miguel Sogbe, Oscar Beloqui, Ana Patiño-García, Vincenzo Cirigliano, Luis Izquierdo.
      Elective Genomic Testing (EGT) can identify individuals at risk for actionable conditions that would not come to clinical attention following current testing guidelines. We describe the results of a checkup unit from a leading Spanish University hospital (Clínica Universidad de Navarra, Spain) that has incorporated EGT to their regular clinical practice. Medical anamnesis, biochemistry, low-intensity whole body scan and EGT with interpretation of over 560 genes related to actionable adult-onset diseases (Veritas Intercontinental, Spain) was performed in 400 participants, including medical consultation before and after the checkup. Clinically relevant variants were identified in 79/400 participants (19.8%). Thirteen individuals (3.3%) presented with clinical variants included in the American College of Medical Genetics and Genomics secondary finding list (ACMG SF list); 69.2% of these variants showed potential association with personal or family history (PFH). The study presents the results of the first hospital integrating EGT into the checkup unit.
    Keywords:  elective genome; genome sequencing; genomic check-up; genomic screening; preventive genomics; preventive medicine
    DOI:  https://doi.org/10.3389/fgene.2025.1722462
  7. Eur J Hum Genet. 2026 Feb 13.
    Impact of a digital platform on genetic counselling encounters in the screening context.
    Chloe Mighton, Alli Jan, Ling Lee, Sophie Bouffler, Lilian Downie, Marc Clausen, Clara Gaff, Yvonne Bombard, Zornitza Stark, Melissa Martyn.
      Digital tools for pre-test education provision and decision support could assist the scalability of opportunistic genomic screening. We evaluated the utility of a digital platform, the Genetics Adviser (GA), for supporting parental decisions about screening for additional findings in the paediatric acute care context. Parents of children who had completed ultrarapid diagnostic genomic testing in the acute setting were offered opportunistic screening following hospital discharge. Interested participants were provided with optional access to GA and offered pre-test genetic counselling (GC). GC sessions were audio-recorded, transcribed verbatim, and participant/counsellor interactions qualitatively analysed to examine the impact of GA use on counselling sessions. Surveys were administered: prior to and after pre-test GC; 1 month after return of results. One hundred and sixty-seven families were offered genomic screening and given access to GA. Family engagement with GA was 52% (87/167) overall, with three-quarters (81/119) of those who attended genetic counselling having engaged with GA. GA use impacted genetic counselling: in consultations where not all parents used GA, more concerns were raised and more questions asked about topics included in GA; GCs also spent more time clarifying values or understanding. GA users correctly answered more knowledge questions at every survey time point. Eighty-three per cent of post-result survey respondents believed GA contained enough information for them to make decisions about opportunistic screening without additional genetic counselling. These findings demonstrate the utility of GA in supporting the scalability of opportunistic genomic screening.
    DOI:  https://doi.org/10.1038/s41431-026-02029-6
  8. J Neurol. 2026 Feb 14. 273(2): 145
    A roadmap for a patient-centred approach to Pompe disease management.
    Benedikt Schoser, Cristina Domínguez-González, Pascal Laforet, Andreas Hahn, Paul Gissen, Anna Kostera-Pruszczyk, Andreas Thalmeier, John Vissing.
       INTRODUCTION: Pompe disease is a rare, progressive genetic disorder caused by pathogenic variants in the GAA gene. Emerging gene therapies offer the potential for long-term disease management, although logistical and clinical challenges demand specialised centres with defined protocols. A scientific steering committee of 8 European experts deliberated on the requirements for establishing gene therapy centres of excellence for Pompe disease.
    METHODS: A modified think-tank approach was used to develop expert-based recommendations through qualitative research utilizing expert opinion methodology. Discussion topics were validated in an online kick-off meeting. Experts were assigned specific topics and tasked with generating content. Multiple online meetings facilitated expert presentations, discussions, and validation of recommendations for each topic.
    RESULTS: Optimised patient management and timely access to treatment require accurate diagnosis and evaluation of Pompe disease. The committee recommended expanding newborn screening programs for infantile-onset Pompe disease and developing protocols for follow-up of presymptomatic late-onset Pompe disease. A specialised multidisciplinary team trained in Pompe disease and gene therapy should manage the patient journey. Pre-gene therapy assessments were recommended to mitigate risks. Patients should be hospitalized and continuously monitored during gene therapy infusions. After gene therapy, guidelines recommend corticosteroid immunosuppression, monitoring for adverse events (including hepatoxicity, myocarditis, thrombocytopenia, thrombotic microangiopathy, and hemophagocytic lymphohistiocytosis), and Pompe disease assessments (including motor functional assessments, magnetic resonance imaging of the muscles, and patient-reported outcomes). Centres of excellence require infrastructure with standard operating procedures for gene therapy products.
    CONCLUSIONS: Implementing gene therapy for Pompe disease requires a coordinated multidisciplinary effort to overcome gaps in knowledge, infrastructure, and patient management.
    Keywords:  Centres of excellence; Gene therapy; Multidisciplinary team; Pompe disease; Rare genetic disorder; Think-tank methodology
    DOI:  https://doi.org/10.1007/s00415-026-13687-3
  9. Semin Oncol Nurs. 2026 Feb 12. pii: S0749-2081(26)00023-9. [Epub ahead of print] 152144
    Impact of Digital Tools on Knowledge, Genetic Counseling, and Testing Uptake: A Systematic Review and Meta-analysis.
    Maide Nur Tümkaya, Şeyma İnciser Paşalak, Memnun Seven.
       OBJECTIVES: This systematic review and meta-analysis aimed to synthesize evidence on the effects of digital genetic tools on completion of pretest counseling, uptake of genetic testing, and knowledge.
    METHODS: The meta-analysis was performed using Review Manager (RevMan 5.4.1) software to synthesize effect sizes. Databases including, PubMed, Web of Science, Ovid MEDLINE, CINAHL, and Scopus were searched. The methodological quality of the studies was assessed using the Cochrane and Joanna Briggs Institute (JBI) critical appraisal checklists.
    RESULTS: Seventeen studies with 6,714 participants were included. Digital interventions significantly increased completion of pretest counseling across four studies (Odds ratio [OR] 2.07, 95% confidence interval [95% CI] 1.22-3.51; Z = 2.70, P = .0007). Genetic testing uptake did not differ between digital and in-person care across seven studies (OR 1.30, 95% CI 0.80-2.10; P = .29; I² = 82%). Knowledge outcomes were comparable for telehealth versus in-person (SMD -0.09, 95% CI -0.40 to 0.23; P = .59); other digital formats suggested greater gains in some settings (SMD 1.19, 95% CI 0.01-2.37; P = .05), though pooled effects were not statistically significant and heterogeneity was substantial.
    CONCLUSIONS: Digital tools are generally noninferior to in-person care for knowledge and psychosocial outcomes and roughly equivalent for genetic test uptake, while doubling the odds of completing pretest counseling.
    IMPLICATIONS FOR NURSING PRACTICE: Digital genetic counseling delivered via telehealth, web-based platforms, and AI-supported tools can expand access to genetic services while maintaining patient-centered care. Nurses play a key role in guiding patients through these technologies and supporting informed, equitable access within digital and hybrid care models.
    REGISTRATION: PROSPERO (CRD420251042666).
    Keywords:  counseling; digital tool; genetic; genetic testing uptake; knowledge
    DOI:  https://doi.org/10.1016/j.soncn.2026.152144
  10. Indian J Pediatr. 2026 Feb 11.
    Perspective - The Role of Peripheral Outreach Programs for Genetic Disorders for Optimizing Healthcare.
    Kuldeep Singh, Amit Kumar Mittal, Tanuja Rajial, Varuna Vyas, Pradeep Dwivedi, Dolat Singh Shekhawat, Pratibha Singh, Siyaram Didel.
      
    Keywords:  Economic burden; Genomic screening; Hereditary disorders; Outreach program; Public health genetics; Rare disorders
    DOI:  https://doi.org/10.1007/s12098-026-06005-2
  11. Adv Sci (Weinh). 2026 Feb 08. e18656
    Genetic Diagnosis and Discovery Enabled by Large Language Models.
    Undiagnosed Diseases Network
      Artificial intelligence (AI) has been used in many areas of medicine, and large language models (LLMs) have shown potential utility for various clinical applications. However, to determine if LLMs can accelerate the pace of genetic diagnosis and discovery, we examined whether recently developed LLMs (Med-PaLM 2 and Gemini) could assist in solving four types of genetic problems with sequentially increasing complexity. First, in response to free-text input, Med-PaLM 2 correctly identified murine genes with experimentally verified causative genetic factors for six previously studied murine models of biomedical traits. Second, Med-PaLM 2 identified a novel causative murine genetic factor for spontaneous hearing loss that was validated using knock-in mice. Third, we developed a retrieval and grounding pipeline that enabled Gemini 2.5 Pro to analyze large lists of genes, which contained genetic variants that were identified in the genomic sequences of 20 human subjects with hearing loss, and demonstrated that it can assist in identifying causative genetic factors for hearing loss. Fourth, we modified the genetic analysis pipeline to enable Gemini 2.5 Pro without any task-specific fine-tuning to identify causative genetic factors for six subjects with rare genetic diseases, which required 14 to 34 different terms to describe their multi-faceted symptom complexes. These results demonstrate that an AI pipeline can facilitate genetic diagnosis and discovery in mice and humans.
    Keywords:  artificial intelligence; genetic discovery; large language model
    DOI:  https://doi.org/10.1002/advs.202518656
This page is being maintained by Thomas Krichel. It was last updated on 2026‒02‒15 at 9:49.