bims-tyki2d 2026-01-11 papers

Issue of 2026–01–11
five papers selected by
Zoya Panahloo, UCB

Genet Med Open. 2026 ;4 103477

Medical genetics needs assessment: An online cross-sectional survey from Nepal.

Pratiksha Gyawali, Binaya Shrestha, Kelly Beharry, Gareema Agarwal, Shane C Quinonez.

Purpose: Medical genetic services remain limited in low- and middle- income countries, such as Nepal, leading to poor health outcomes for individuals affected by genetic disorders. This study aimed to assess perspective and characterize current practices and attitudes toward genetic services among health care providers in Nepal.
Methods: A web-based survey was completed by 131 clinicians across multiple disciplines, exploring participant demographics, experience with genetic services, and perceived barriers to genetic testing and counseling.
Results: Although 42% of respondents reported regularly caring for patients with suspected genetic disorders, 77% of providers reported difficulties with obtaining genetic testing. The most frequently cited barriers included limited laboratory availability (28%), cost (26%), and logistical challenges (19%). Many respondents reported confidence in discussing disease recurrence risk (63%), treating genetic disorders (40%), and providing genetic counseling (48%), and the majority (86%) expressed interest in furthering their genetic education because only 19% felt their current genetics knowledge was sufficient.
Conclusion: This study highlights a clear demand for accessible, affordable, in-country genetic services in Nepal and underscores the need for investment in clinical training and capacity building to improve access and outcomes for patients with genetic disorders.

Keywords: Capacity building; Genetic disorders; Genetic services; Needs assessment; Nepal

DOI: https://doi.org/10.1016/j.gimo.2025.103477

WMJ. 2025 ;124(5): 467-470

A Statewide Approach to Collaboratively Improve Access to Medical Genetics Services in Wisconsin.

Sara Zoran, Jessica Scott Schwoerer.

BACKGROUND: In the absence of a state-led initiative to monitor and address medical genetics issues affecting Wisconsin, a collaborative approach among stakeholders was implemented to identify and address service needs.
METHODS: Surveys and consensus-building tools were employed to identify priority service-access needs and establish strategies to address these needs.
RESULTS: Four statewide medical genetics priorities were identified: (1) improved coordination and collaboration, (2) increased funding for the Newborn Screening Program, (3) Medicaid policy changes regarding inpatient genomic testing and reimbursement for outpatient genetic counseling services, and (4) educational opportunities for nongenetic providers to incorporate genomic medicine into practice. Three workgroups were formed and remain active in advanced efforts in these areas.
DISCUSSION: A stakeholder-driven process supported engagement, shared communication, and collaboration within the Wisconsin medical genetics community. Workgroups facilitated measurable progress, including increased newborn screening funding, advancement of administrative rules, expanded educational opportunities, and ongoing policy advocacy. Survey findings underscore the need for improved statewide communication and continued attention to funding and telehealth policy.
CONCLUSIONS: This initiative demonstrates an efficient and effective approach to advancing statewide collaboration and policy change in medical genetics. Sustained engagement will be critical to ensure equitable access to genetic services across Wisconsin.

Neuroscience. 2026 Jan 05. pii: S0306-4522(26)00001-1. [Epub ahead of print]595 171-186

Tk2 deficiency-mediated mitochondrial dysfunction drives neuroinflammation and seizure frequency in epilepsy.

Xi Zhang, Jiahao Lian, Yongbin Pang, Haohao Cui, Xiaobo Ye, Qiang Meng, Yong Liu, Huanfa Li, Yutao Ren, Ying Zhang, Hua Zhang, Hao Wu.

Seizure frequency is a key indicator of disease severity and treatment response in epilepsy, yet its molecular determinants remain unclear. We performed proteomic profiling of resected epileptogenic brain tissue from patients, stratified by seizure frequency and by temporal versus extratemporal origin, and functionally validated candidate differentially expressed proteins (DEPs). Seizure foci of high and low frequencies in distinct brain regions displayed region-specific proteomic profiles. However, bioinformatic analyses of both temporal and extratemporal cohorts consistently showed that the down-regulated proteins converge on mitochondrial localization and function. Among these, mitochondrial thymidine kinase 2 (Tk2) exhibited a robust inverse correlation with seizure frequency, a finding confirmed in patient tissues across different frequency groups. Consistently, Tk2 expression was reduced across multiple brain regions in two seizure models induced by pilocarpine or ferric chloride. Mechanistically, loss of Tk2 activated the cGAS-STING pathway, upregulated inflammatory genes, and then increased seizure susceptibility. These findings identify Tk2 as a mitochondrial kinase that couples energetic failure to neuroinflammation, and provide a mechanistic basis for targeting the Tk2-mitochondria-inflammation axis in epilepsy.

Keywords: Epilepsy; Metabolism inflammation; Molecular biomarkers; Proteomics

DOI: https://doi.org/10.1016/j.neuroscience.2026.01.001

Am J Med Genet C Semin Med Genet. 2026 Jan 07.

CURE ID: A Platform to Collect Real-World Treatment Data for Drug Repurposing in Rare Genetic Disorders.

Tahsin Farid, Maura R Z Ruzhnikov, Mili Duggal, Keyla C Tumas, Shira Strongin, Eric Sid, Sarah R Fuchs, Leonard Sacks, Dominique C Pichard, Catherine Pilgrim-Grayson, Ewy A Mathé, Heather A Stone.

Rare diseases collectively affect millions of Americans, but less than 5% have approved treatments, and new drug development remains limited. For such diseases, drug repurposing may be an effective strategy to find new treatment options. In the rare genetic disorder community, drugs are frequently prescribed off-label. This information is rarely available for research, but if captured, could be leveraged to accelerate the identification of candidate drugs to be evaluated for safety and efficacy of the treatment of rare diseases. CURE ID is a publicly available treatment registry that collects real-world treatment data directly from healthcare providers, patients, and care partners in a consistent format. By aggregating this information, CURE ID can generate hypotheses for follow-up targeted research of repurposed drugs, potentially leading to the approval of these drugs for new indications. The success of the platform is predicated on its adoption in the rare disease community and routinely reporting treatment experiences to CURE ID.

Keywords: CURE ID; drug repurposing; rare diseases; rare genetic disorders; real‐world data

DOI: https://doi.org/10.1002/ajmg.c.32153

Open Res Eur. 2025 ;5 74

Sharing behavior and health care utilization following direct-to-consumer genetic testing: a systematic review.

Eva Van Steijvoort, Kaatje Goossens, Kenji Demesure, Alexandra Stanczak, Maria Siermann, Pascal Borry.

Background: Direct-to-consumer genetic testing (DTC-GT) which provides genetic information directly to the public, has become widely available at a moderate cost. Since DTC-GT companies frequently recommend that consumers consult healthcare professionals for assistance in interpreting and using genetic health risk information, this could potentially have an impact on healthcare systems.
Methods: We performed a systematic review to assess: (1) the sharing behavior of actual DTC-GT consumers, (2) experiences of healthcare professionals regarding DTC-GT consumers sharing their test results and (3) healthcare utilization following DTC-GT, with a particular focus on validation of DTC-GT results and subsequent clinical actions. Our systematic review was registered in PROSPERO under the registration number CRD42024517079.
Results: Our search identified 40 unique articles eligible for inclusion that were published between 2009 en 2022. The proportion of participants who shared their DTC-GT test results with a health care professional ranged from 1% to 57%. DTC-GT consumers most commonly reported sharing their results with a primary healthcare professional. The proportion of health care professionals that had experiences with DTC-consumers sharing their test results ranged from 19% to 76%. The percentage of participants sharing their DTC-GT test with family members ranged from 18% to 98%. More detailed analysis indicated that this was frequently the case with partners, parents, and siblings. Sharing of test results with extended family members occurred less frequently. Several studies reported on instances of DTC-GT result validation and clinical actions performed based on the DTC-GT findings.
Conclusion: Conclusion While initial concerns about the impact of DTC-GT on health care systems have not fully materialized, the increasing number of consumers consulting with healthcare professionals underscores the need for preparedness and appropriate policy responses. Future research should prioritize standardizing study methodologies and expanding investigations beyond the U.S. context to better capture the global impact of DTC-GT.

Keywords: Direct to consumer; Genetic testing; Genomics; Predictive Testing; Prevention; Public Health; Screening

DOI: https://doi.org/10.12688/openreseurope.19751.2