Genetics in Medicine Open最新文献

{"title":"P057: Incidence and phenotypic spectrum of SDHA pathogenic variants identified in an unselected precision medicine cohort*","authors":"Alexandra Capasso , Anuja Chitre , Katherine Roth , Joseph Bonner , Stacy Gray , Stephen Gruber , Heather Hampel , Christine Hong , Kevin McDonnell , Bita Nehoray , Ilana Solomon , Joanne Jeter","doi":"10.1016/j.gimo.2026.103548","DOIUrl":"10.1016/j.gimo.2026.103548","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103548"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395066","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":"P004: Expanding the clinical and functional spectrum of NUS1-CDG: Insights from systematic phenotyping using NPCRS and ICARS*","authors":"Daniel Schecter , Georgia MacDonald , Tamas Kozciz , Eva Morava-Kosicz","doi":"10.1016/j.gimo.2026.103495","DOIUrl":"10.1016/j.gimo.2026.103495","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103495"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395376","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":"P065: Cell-free testing reliably detects DPYD and UGT1A1 PGx alterations, improving chemotherapy dosing and clinical yield*","authors":"Robert Huether , Christopher Vlangos , Yan Yang , Karl Beutner , Robert Tell , Jason Blue-Smith , Wei Zhu","doi":"10.1016/j.gimo.2026.103556","DOIUrl":"10.1016/j.gimo.2026.103556","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103556"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396168","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":"P055: Successful utilization of immune tolerance induction in a pediatric patient with classic Fabry disease: A case report","authors":"Mary Riedy , Nina Zheng , Katherine Tuttle , Jillian Soler , Stephanie McMahon , Nicholas Farris , Ankit Desai , Priya Kishnani , Eran Tallis","doi":"10.1016/j.gimo.2026.103546","DOIUrl":"10.1016/j.gimo.2026.103546","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103546"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396215","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":"Clinical risk factors predicting likelihood of pathogenic genetic result in NICU patients","authors":"Joshua L. Bonkowsky ,&nbsp;Samuel B. Zoucha ,&nbsp;Jenna Jensen ,&nbsp;Jacob Wilkes ,&nbsp;Rachel N. Palmquist ,&nbsp;Mark Yandell ,&nbsp;Martin Tristani-Firouzi","doi":"10.1016/j.gimo.2026.104370","DOIUrl":"10.1016/j.gimo.2026.104370","url":null,"abstract":"<div><h3>Purpose</h3><div>Children with neonatal intensive care unit (NICU) admission have higher rates of genetic disease, but it is unclear which patients should have genetic testing. Our goal was to identify clinical predictors associated with a pathogenic genetic result in NICU infants.</div></div><div><h3>Methods</h3><div>This was a retrospective, population-based cohort analysis of infants born between January 1, 2009 and June 30, 2011 with a history of NICU admission and subsequent follow-up and genetic testing through 2021.</div></div><div><h3>Results</h3><div>A total of 99 infants met inclusion criteria. In total, 64 (65%) patients had a negative genetic test result; 35 (35%) had a positive (pathogenic) result. Lower birthweight, younger gestational age, longer length of stay, or 2 or more indicators of severe illness were associated with a pathogenic result.</div></div><div><h3>Conclusion</h3><div>Our work suggests that clinical predictors can be used to guide genetic testing in NICU infants. Use of these clinical risk factors could provide a diagnostic care pathway, potentially shortening the diagnostic odyssey and reducing potential morbidities.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104370"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396670","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":"P026: Neurobehavioral profiles in primary mitochondrial disorders: Overview of select cases from a single center multi-disciplinary mitochondrial disorders program","authors":"Kuntal Sen ,&nbsp;Ana Moreno Chaza ,&nbsp;Srika Amin ,&nbsp;Amy LaCava ,&nbsp;Sinan Turnacioglu","doi":"10.1016/j.gimo.2026.103517","DOIUrl":"10.1016/j.gimo.2026.103517","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103517"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396774","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":"Evidence of variations in genetic prevalence for loss-of-function PKP2 variants between individuals with European and African ancestry","authors":"Alexandra Winters ,&nbsp;Renae Judy ,&nbsp;Choudhary Anwar A. Chahal ,&nbsp;Ghaith Sharaf Dabbagh ,&nbsp;Ravi A. Shah ,&nbsp;Scott Damrauer ,&nbsp;Melissa A. Kelly ,&nbsp;Cynthia A. James ,&nbsp;Crystal Tichnell ,&nbsp;Brittney Murray ,&nbsp;Diane Smelser ,&nbsp;H. Shanker Rao ,&nbsp;David J. Carey ,&nbsp;Christopher M. Haggerty ,&nbsp;Eric D. Carruth","doi":"10.1016/j.gimo.2026.104397","DOIUrl":"10.1016/j.gimo.2026.104397","url":null,"abstract":"<div><h3>Purpose</h3><div>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition associated with increased risk for ventricular arrhythmias and sudden cardiac death. Prior ARVC studies contained majority European-ancestry individuals; however, limited data have shown an increase in disease-associated variants in individuals of African ancestry. This study aimed to assess genotype/phenotype differences by ancestry across several cohorts.</div></div><div><h3>Methods</h3><div>We analyzed genomic and health record data from over 660,000 individuals from 4 population biobanks. We compared the prevalence of predicted pathogenic variants in 4 ARVC-associated genes across ancestries and the association with ARVC-related traits.</div></div><div><h3>Results</h3><div>We observed that individuals with a <em>PKP2</em> predicted pathogenic variant were 2 to 3 times as likely to be of African ancestry than European ancestry in MyCode, All of Us, and the UK Biobank. This difference was not seen in the Penn Medicine Biobank (PMBB). <em>PKP2</em> predicted pathogenic heterozygotes were more likely to have an ARVC-related trait in the MyCode and All of Us cohorts but not in PMBB or UK Biobank.</div></div><div><h3>Conclusion</h3><div>Although individuals of African ancestry are more likely to carry a <em>PKP2</em> predicted pathogenic variant, only European ancestry heterozygotes in MyCode and All of Us had increased odds of an ARVC-related trait, suggesting reduced penetrance or clinical underrecognition of disease in individuals of African ancestry.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104397"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797526","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":"RecQ DNA helicases germline variants in Lynch-like syndrome","authors":"Mar Giner-Calabuig ,&nbsp;Seila De Leon ,&nbsp;Gemma Vidal-Pedrola ,&nbsp;Tara D. Fehlmann ,&nbsp;Chinedu Ukaegbu ,&nbsp;Joanna Gibson ,&nbsp;Miren Alustiza Fernandez ,&nbsp;Maria-Dolores Pico ,&nbsp;Cristina Alenda ,&nbsp;Josep Reyes ,&nbsp;Silvia P. Ortega ,&nbsp;Antònia Obrador-Hevia ,&nbsp;Sapna Syngal ,&nbsp;Elena Stoffel ,&nbsp;Nathan A. Ellis ,&nbsp;Adela Castillejo ,&nbsp;José Luis Soto ,&nbsp;Rodrigo Jover ,&nbsp;Xavier Llor ,&nbsp;Rosa M. Xicola","doi":"10.1016/j.gimo.2026.104400","DOIUrl":"10.1016/j.gimo.2026.104400","url":null,"abstract":"<div><h3>Purpose</h3><div>Lynch-like syndrome (LLS) is associated with an incomplete understanding of its molecular basis. Some LLS tumors harbor somatic variants in mismatch repair genes, whereas germline variants in other DNA repair genes point to a hereditary predisposition in certain cases. Clinically, LLS patients tend to develop colorectal cancer (CRC) earlier, have a stronger family history of CRC, and respond better to immunotherapy compared with sporadic CRC cases. This study seeks to identify cancer-susceptibility genes in LLS patients, which could affect diagnosis, treatment, and surveillance.</div></div><div><h3>Methods</h3><div>Germline exome sequencing was performed on 102 participants, including 14 previously reported cases. In vitro models were created to study the effect of loss-of-function (LoF) variants in DNA repair genes. Gene/protein expression was evaluated using quantitative real-time PCR and Western blotting, and DNA repair capacity was assessed via H2AX phosphorylation after ionizing radiation exposure.</div></div><div><h3>Results</h3><div>Nine rare LoF variants were identified in DNA repair genes, including 3 in RecQ DNA helicases (<em>WRN</em> HGNC:12791<em>, RECQL5</em> HGNC:9950). LLS patients had a higher mutational burden in DNA repair genes across various cancer phenotypes. In vitro, cells with these LoF variants showed reduced gene-protein expression and increased H2AX phosphorylation after irradiation, indicating impaired DNA repair.</div></div><div><h3>Conclusion</h3><div>A single LoF variant in RecQ DNA helicase genes can result in significant DNA repair deficiency, leading to genomic instability and contributing to CRC development in LLS. Therefore, we present evidence for incorporating <em>RECQL5</em> into genetic testing panels for CRC risk assessment, which would enhance both diagnosis and treatment outcomes.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104400"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184300","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":"The landscape of variants in pre-mRNA-processing factor genes in an Irish cohort","authors":"Laura K. Finnegan,&nbsp;Anna R. Ridgeway,&nbsp;Matthew Carrigan,&nbsp;Hilary Dempsey,&nbsp;Róisín Long,&nbsp;Evan Matthews,&nbsp;Daan Panneman,&nbsp;Jacqueline Turner,&nbsp;Adrian Dockery,&nbsp;Laura Whelan,&nbsp;Ciara Shortall,&nbsp;Ella Kopčić,&nbsp;Frans P.M. Cremers,&nbsp;Susanne Roosing,&nbsp;Claire Kirk,&nbsp;Giuliana Silvestri,&nbsp;David Keegan,&nbsp;Paul F. Kenna,&nbsp;Emma Duignan,&nbsp;Naomi Chadderton,&nbsp;G. Jane Farrar","doi":"10.1016/j.gimo.2026.104402","DOIUrl":"10.1016/j.gimo.2026.104402","url":null,"abstract":"<div><h3>Purpose</h3><div>Variants in pre-messenger RNA (mRNA) processing genes account for ∼15% to 20% of autosomal dominant retinitis pigmentosa, causing severe vision loss. We provide an in-depth characterization of pre-mRNA-processing variants in the population, with a focus on genotype-phenotype correlations.</div></div><div><h3>Methods</h3><div>Participants underwent next-generation sequencing, variant filtering and interpretation. Impact(s) on protein structure/function were predicted through AlphaFold, ColabFold, among others. Clinical information was collated and segregation analysis undertaken. Variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines.</div></div><div><h3>Results</h3><div>A total of 635 patients with retinitis pigmentosa (RP) were screened. Notably, 36 different variants were identified in <em>PRPF31</em>, <em>PRPF8</em>, <em>SNRNP200</em>, <em>PRPF3</em>, <em>RP9</em>, and <em>PRPF</em><em>6</em>; 19 were classified as likely pathogenic/pathogenic. Thirteen of 36 variants were absent from PubMed, gnomAD, LOVD, and ClinVar, with an additional 10 not previously associated with retinal degeneration. Genotype-phenotypes correlations were illuminated; variants in PRPF genes caused more severe retinal degeneration than <em>SNRNP200</em> variants.</div></div><div><h3>Conclusion</h3><div>We provide a detailed overview of the genetic landscape of variants in pre-mRNA-processing factor genes in Ireland, accounting for 14% of genetically solved autosomal dominant retinitis pigmentosa cases. Results highlight significant genetic diversity between populations, mutational diversity inherent in inherited retinal degenerations and the role of variants in mRNA-processing genes as causative of devastating ocular disorders.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104402"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392864","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":"Methodology of DNA extraction and sequencing from living cardiomyocytes collected by catheter in humans","authors":"Flavie Ader ,&nbsp;Céline Guilbeau-Frugier ,&nbsp;Emeline Lhuillier ,&nbsp;Frédéric Martins ,&nbsp;Anne Alicia Gonzalez ,&nbsp;Anne Rollin ,&nbsp;Maxime Beneyto ,&nbsp;Céline Gales ,&nbsp;Filipe Pires ,&nbsp;Jean-José Maoret ,&nbsp;Jean-Michel Sénard ,&nbsp;Jean Timnou-Bekouti ,&nbsp;Eric Villard ,&nbsp;Laetitia Duboscq-Bidot ,&nbsp;Estelle Gandjbakhch ,&nbsp;Philippe Maury","doi":"10.1016/j.gimo.2025.103473","DOIUrl":"10.1016/j.gimo.2025.103473","url":null,"abstract":"<div><h3>Purpose</h3><div>We present here the technical feasibility of percutaneously retrieving cardiomyocytes (CMs) through the lumen of irrigated ablation catheters, with the aim of obtaining DNA of sufficient quality/quantity for allowing DNA amplification, screening, and derived genetic analysis.</div></div><div><h3>Methods</h3><div>Irrigated conventional catheters for ablation were used for creating endocardial right ventricular voltage maps in 38 patients with suspected or proved arrhythmogenic right ventricular cardiomyopathy. Blood material was collected from scar areas by aspiration and filtered, CMs detected by light microscopy were aspirated, centrifugated, and freezed.</div><div>DNA was extracted, amplified, and sequenced, and variants were compared with variants obtained from leukocyte DNA.</div></div><div><h3>Results</h3><div>At least 1 CM was obtained in 95% of patients (median 11 CM/patient). After refinements of the technique, a total of 136 samples (22 patients) allowed DNA extraction and amplification, successful in 60% of samples (16 patients). DNA capture sequencing of a panel of cardiomyopathy-associated genes was successfully performed in 14 patients and compared with blood sequencing in 11. After controlled by Sanger, an additional variant, not present in blood, has been confirmed in CM in one patient.</div></div><div><h3>Conclusion</h3><div>This new mini-invasive technique of sampling allows to perform genetic analysis on CMs. Pending future improvements, this technique could provide new sources of human cells for research and potential mosaicism detection.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103473"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145841210","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}