Genetics in Medicine Open最新文献

{"title":"P025: Impact of health-system specialty pharmacy utilization on sapropterin adherence in patients with phenylketonuria (PKU)","authors":"Mary Riedy , Derek Rossetti , Priya Duraisamy , Jessica Kozakiewicz , Nicole Acquisto , Calvin Meaney","doi":"10.1016/j.gimo.2026.103516","DOIUrl":"10.1016/j.gimo.2026.103516","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103516"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P019: Mitophagy as a developmental pathology in the cardiac phenotype of Barth syndrome","authors":"Madison Santizo , Olivia Sniezek-Carney , Hilary Vernon","doi":"10.1016/j.gimo.2026.103510","DOIUrl":"10.1016/j.gimo.2026.103510","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103510"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P024: A pilot phase 2 study to assess the safety and efficacy of sirolimus in pediatric Leigh syndrome patients: Interim analysis","authors":"Matt Demczko , Marissa Weis , Sara Nguyen , Laura MacMullen , Amy Goldstein , Marni Falk , Zarazuela Zolkipli-Cunningham","doi":"10.1016/j.gimo.2026.103515","DOIUrl":"10.1016/j.gimo.2026.103515","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103515"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early initiation of enzyme replacement therapy as facilitated by newborn screening improves health outcomes among patients with infantile-onset Pompe disease","authors":"Ankit K. Desai ,&nbsp;Eleanor Rodriguez-Rassi ,&nbsp;Suhag Parikh ,&nbsp;Rossana Sanchez Russo ,&nbsp;David Kronn ,&nbsp;J. Austin Hamm ,&nbsp;Irene J. Chang ,&nbsp;Damara Ortiz ,&nbsp;Molly McPheron ,&nbsp;Holly Lydigsen ,&nbsp;Stephanie DeArmey ,&nbsp;Sarah P. Young ,&nbsp;Priya S. Kishnani","doi":"10.1016/j.gimo.2025.103478","DOIUrl":"10.1016/j.gimo.2025.103478","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the benefits of early enzyme replacement therapy (ERT) in patients with infantile-onset Pompe disease (IOPD).</div></div><div><h3>Methods</h3><div>A retrospective chart review of 17 IOPD (7 cross-reactive immunologic material [CRIM]-negative and 10 CRIM positive) who initiated ERT (alglucosidase alfa) ≤4 weeks of age and had ≥18 months follow-up was performed.</div></div><div><h3>Results</h3><div>Patients received starting doses of 20 mg/kg/every other week (<em>n</em> = 11), 20 mg/kg/week (<em>n</em> = 3), or 40 mg/kg/week (<em>n</em> = 3). Six CRIM-negative and 2 patients who were CRIM positive received immune tolerance induction (ITI) with Rituximab+Methotrexate+intravenous immunoglobulin. Five patients who were CRIM positive received transient low-dose methotrexate. All CRIM-negative patients were immune tolerant. Three patients who were CRIM positive developed high-sustained antibody titers (HSAT); 2 were immune tolerant after bortezomib-based ITI. One patient who was CRIM positive developed HSAT, was invasively ventilated, and succumbed at age 5.2 years. At the most recent follow-up (MRFU; 3.1-18.4 years), 16 patients were alive, ambulatory, feeding orally, invasive ventilator-free, and receiving high-dose ERT (median lifelong dose 2.76X; 1.36-4.00). All patients experienced left ventricular mass index and Glc₄ reductions and for a subset, biomarkers were within normal limits at MRFU (left ventricular mass index:16/17, AST:9/17, CK:5/17, and Glc₄:5/16).</div></div><div><h3>Conclusion</h3><div>These data highlight the benefits of early ERT initiation and ITI, along with high-dose ERT. Despite early treatment, patients with IOPD remain at risk of developing HSAT.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103478"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145841211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid targeted analysis of the genome: Rapid genomic sequencing in critically ill infants","authors":"K. Taylor Wild ,&nbsp;Sara L. Reichert ,&nbsp;Matthew C. Dulik ,&nbsp;Alexandra Heck ,&nbsp;Emma C. Bedoukian ,&nbsp;Kathleen H. Wood ,&nbsp;Katharine P. Callahan ,&nbsp;Jennifer A. Hershey ,&nbsp;David A. Munson ,&nbsp;Kieran B. Pechter ,&nbsp;Kelly Regan-Fendt ,&nbsp;Anthony M. Gacita ,&nbsp;Francis Jeshira Reynoso Santos ,&nbsp;Morgan L. McManus ,&nbsp;Natalie Burrill ,&nbsp;Maria Alejandra Diaz-Miranda ,&nbsp;Melissa A. Gilbert ,&nbsp;Ian D. Krantz ,&nbsp;Ramakrishnan Rajagopalan ,&nbsp;Laura K. Conlin ,&nbsp;Nancy B. Spinner","doi":"10.1016/j.gimo.2025.103476","DOIUrl":"10.1016/j.gimo.2025.103476","url":null,"abstract":"<div><h3>Purpose</h3><div>We developed a genome sequencing-based test (Rapid Targeted Analysis of the Genome for Infants [rTAG-I]) to minimize turnaround time while maximizing diagnostic yield and access to rapid sequencing for critically ill infants. We sought to create a system of predicting which infants would have a molecular finding.</div></div><div><h3>Methods</h3><div>We performed a prospective observational study of infants referred for genetics consult who received rTAG-I testing, which analyzes 3183 curated genes with phenotype-agnostic prioritization of pathogenic and likely pathogenic variants. Infants were stratified by perceived likelihood of a diagnostic result and divided into “Likely,” “Uncertain,” and “Not Likely.” We also assessed whether reportable findings correlated with patient phenotypes.</div></div><div><h3>Results</h3><div>We identified reportable findings in 133/400 (33%) infants. Access to rapid testing increased from 1% to 20% of all infants hospitalized in the neonatal/infant intensive care unit and cardiac intensive care unit, with a median turnaround time of 4.9 days. rTAG-I performed as well as exome/genome sequencing. Clinically associated results were identified in 59% of the “Likely” group and 9% of the “Not Likely” group.</div></div><div><h3>Conclusion</h3><div>rTAG-I produced a high rate of reportable findings with a rapid turnaround time. Our ability to predict infants who would benefit most was imperfect, reinforcing that broad access to genome-based testing is still required.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103476"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Not “just a VUS”","authors":"Christina G. Tise ,&nbsp;Sophia M. Adelson ,&nbsp;Elizabeth B. Garrity ,&nbsp;Devon E. Bonner","doi":"10.1016/j.gimo.2026.104401","DOIUrl":"10.1016/j.gimo.2026.104401","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104401"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socioeconomic and clinical factors associated with genetic testing completion in Stargardt disease","authors":"Dorothy T. Wang,&nbsp;Bani Antonio-Aguirre,&nbsp;Annabelle Pan,&nbsp;Maria Ludovica Ruggeri,&nbsp;Setu P. Mehta,&nbsp;Christy H. Smith,&nbsp;Kelsey S. Guthrie,&nbsp;Carolyn Applegate,&nbsp;Jefferson J. Doyle,&nbsp;Mandeep S. Singh","doi":"10.1016/j.gimo.2026.104481","DOIUrl":"10.1016/j.gimo.2026.104481","url":null,"abstract":"<div><h3>Purpose</h3><div>Genetic testing (GT) is crucial for Stargardt disease (STGD) diagnosis and clinical trial (CT) eligibility; however, predictors of GT completion remain understudied. We identified factors associated with GT completion and characterized CT participation among genetically confirmed patients.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 280 patients with clinically diagnosed STGD who were evaluated at a US tertiary referral center (2003-2024). Multivariable logistic regression was used to identify predictors of GT completion.</div></div><div><h3>Results</h3><div>Among 280 participants, 246 (88%) completed GT. GT completion was significantly less likely in participants who were Black (odds ratio [OR]: 0.40, 95% CI: 0.16-0.98), under/uninsured (OR: 0.47, 95% CI: 0.19-0.97), without genetic counseling (GC) (OR: 0.09, 95% CI: 0.03-0.22), or without reproductive plans (OR: 0.35, 95% CI: 0.14-0.89). Clinical factors (eg, age of onset, visual acuity, and family history) showed no significant associations. Common reasons for noncompletion included loss to follow-up (41%), patient refusal (26%), and awaiting GC (24%). Among 223 <em>ABCA4-</em>positive participants, 45 (20%) enrolled in CTs, with most (91%) completing GC.</div></div><div><h3>Conclusion</h3><div>Despite high overall GT completion rates, significant racial and socioeconomic disparities exist. GC emerged as the strongest modifiable factor, conferring over 10-fold higher odds of GT completion. Socioeconomic barriers drive testing disparities in STGD, rather than disease severity or clinical characteristics.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104481"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148735615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline POT1 variants are associated with long telomeres and an unexpected broad spectrum of malignancies","authors":"Aasem Abu Shtaya,&nbsp;Shahar Aloni,&nbsp;Marina Eskin-Schwartz,&nbsp;Nethanel Asher,&nbsp;Noy Azulay,&nbsp;Lina Basel-Salmon,&nbsp;Lily Bazak,&nbsp;Rinat Bernstein Molho,&nbsp;Liza Douiev,&nbsp;Sarit Farage Barhom,&nbsp;Eitan Friedman,&nbsp;Ofer Isakov,&nbsp;Ahmad Mahamid,&nbsp;Orli Michaeli,&nbsp;Inbal Kedar,&nbsp;Zohar Levi,&nbsp;Sari Liberman,&nbsp;Shikma Mordechai,&nbsp;Ofer Reiter,&nbsp;Gili Reznick Levi,&nbsp;Yael Goldberg","doi":"10.1016/j.gimo.2026.104483","DOIUrl":"10.1016/j.gimo.2026.104483","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to expand the clinical and biological understanding of <em>POT1</em> tumor predisposition syndrome and raise awareness of its broad tumor spectrum and association with ultralong telomeres.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of 44 individuals carrying pathogenic or likely pathogenic <em>POT1</em> variants identified between 2018 and 2025. Clinical, pathologic, and demographic data were extracted from medical records. Telomere length was assessed using in-gel hybridization of telomeric restriction fragments.</div></div><div><h3>Results</h3><div>Of 44 heterozygotes, 31 had the c.233T&gt;C; p.(Ile78Thr) variant, 8 had c.1672dup; p.(Tyr558Leufs∗6), and 5 had other frameshifting, likely loss-of-function variants. Cancer was diagnosed in 27 heterozygotes (61%), totaling 84 primary malignancies (range: 0-8 per person), with most cases (79%) occurring after the age of 50 years. Melanoma (34%) and breast cancer in females (45%) were the most common. Additional tumors included papillary thyroid carcinoma, desmoid tumors, and diverse malignant and benign neoplasms. Colonic polyps were frequent. <em>POT1</em> heterozygotes with the p.(Ile78Thr) variant exhibited significantly longer telomeres than control participants, with a 62-year-old woman showing comparable or even longer telomeres than her children.</div></div><div><h3>Conclusion</h3><div><em>POT1</em> pathogenic variants confer susceptibility to a wide tumor spectrum, notably melanoma and, unexpectedly, breast cancer. At least some of these variants are linked to ultralong telomeres, consistent with findings from this study and others. These findings support incorporating <em>POT1</em> into multigene panels and suggest telomere length as a potential biomarker for diagnosis.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104483"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148770127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P029: Reproductive outcomes in the PHEFREE Rare Disease Consortium for phenylketonuria","authors":"Georgianne Arnold ,&nbsp;Hadley Morotti ,&nbsp;Gerard Berry ,&nbsp;Shawn Christ ,&nbsp;Dorothy Grange ,&nbsp;Elaina Jurecki ,&nbsp;Uta Lichter-Konecki ,&nbsp;Harvey Levy ,&nbsp;Nicola Longo ,&nbsp;Stephanie Sacharow ,&nbsp;Brian Shayota ,&nbsp;Janet Thomas ,&nbsp;Desiree White","doi":"10.1016/j.gimo.2026.103520","DOIUrl":"10.1016/j.gimo.2026.103520","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103520"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P056: Diagnosis of multiple Acyl-CoA dehydrogenase deficiency (MADD) with absent EFTB expression and negative genome sequencing","authors":"Yutaka Furuta ,&nbsp;Kaitlyn Bloom ,&nbsp;Jerry Vockley ,&nbsp;Angela Grochowsky ,&nbsp;Neena Agrawal ,&nbsp;Ellen Strickler ,&nbsp;Natalie Owen ,&nbsp;Erica Gray ,&nbsp;B. Lakshitha Perera ,&nbsp;Eric Gamazon ,&nbsp;Lynette Rives ,&nbsp;Rizwan Hamid ,&nbsp;Joy Cogan ,&nbsp;John Phillips ,&nbsp;Thomas Cassini ,&nbsp;Bryce Schuler","doi":"10.1016/j.gimo.2026.104359","DOIUrl":"10.1016/j.gimo.2026.104359","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104359"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}