Genetics in Medicine Open最新文献

{"title":"Pilot implementation study of a default genetic referral process for patients with early-onset colorectal cancer","authors":"Kelsey S. Lau-Min ,&nbsp;Shavon Rochester ,&nbsp;Megan Grabill ,&nbsp;Jessica M. Long ,&nbsp;Danielle B. McKenna ,&nbsp;Jacqueline Powers ,&nbsp;Danny Bracy ,&nbsp;Leland Boisseau ,&nbsp;Peter Gabriel ,&nbsp;Randall Oyer ,&nbsp;Susan M. Domchek ,&nbsp;Katharine A. Rendle ,&nbsp;Katherine L. Nathanson ,&nbsp;Bryson W. Katona","doi":"10.1016/j.gimo.2024.101902","DOIUrl":"10.1016/j.gimo.2024.101902","url":null,"abstract":"<div><h3>Purpose</h3><div>Early-onset colorectal cancer (CRC) diagnosed under age 50 is increasing at alarming rates, with &gt;75% of early-onset cases occurring in patients between 40 and 49 years old. Germline genetic risk evaluations are key to delivering high-quality care to these patients.</div></div><div><h3>Methods</h3><div>We conducted a single-arm pilot implementation study of a default genetic referral process for patients diagnosed with CRC between ages 40 and 49 at 5 hospitals in an academic health system. A research coordinator notified patients and their oncologists of their eligibility for a default genetic referral, after which all patients who did not opt out were referred for genetic counseling, testing, and result disclosure as per usual care. The primary outcome was the genetic referral rate; secondary outcomes included the percentage of eligible patients who were scheduled for a genetic evaluation, completed genetic counseling, and underwent testing within 3 months of the initial referral. We conducted semistructured exit interviews with a subset of patients and oncologists to elicit feedback on the intervention.</div></div><div><h3>Results</h3><div>We included 53 patients, of whom 49 (92%) were referred to genetics, 38 (72%) were scheduled, 22 (42%) completed genetic counseling, and 13 (25%) underwent testing within 3 months of the initial referral. In exit interviews (<em>n</em> = 10 patients and 10 oncologists), participants reported finding the default genetic referral process acceptable and feasible to implement.</div></div><div><h3>Conclusion</h3><div>A default genetic referral process is acceptable, feasible, and associated with a high referral rate for patients with early-onset CRC; however, subsequent scheduling, evaluation, and testing rates remain suboptimal.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 101902"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082992","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":"An evaluation of genetic predisposition to congenital anomalies and pediatric cancer supports KAT6B as a novel neuroblastoma susceptibility gene","authors":"Hyunjung Gu ,&nbsp;Yao Yu ,&nbsp;Saumya Dushyant Sisoudiya ,&nbsp;Pamela Mishra ,&nbsp;He Li ,&nbsp;Jeremy M. Schraw ,&nbsp;Michael E. Scheurer ,&nbsp;Donna M. Muzny ,&nbsp;Danielle Mitchell ,&nbsp;Olga Taylor ,&nbsp;Shalini N. Jhangiani ,&nbsp;Shannon Dugan-Perez ,&nbsp;Yifan Wu ,&nbsp;Harsha Doddapaneni ,&nbsp;Sravya Venkata Bhamidipati ,&nbsp;Marie-Claude Gingras ,&nbsp;Jennifer E. Posey ,&nbsp;Richard A. Gibbs ,&nbsp;Chad D. Huff ,&nbsp;Sharon E. Plon ,&nbsp;Aniko Sabo","doi":"10.1016/j.gimo.2024.101901","DOIUrl":"10.1016/j.gimo.2024.101901","url":null,"abstract":"<div><h3>Purpose</h3><div>Although congenital anomalies are among the strongest risk factors for developing pediatric cancer, the genetic underpinnings remain unclear. Therefore, we evaluated germline susceptibility in children with congenital anomalies and cancer.</div></div><div><h3>Methods</h3><div>Through the Genetic Overlap Between Anomalies and Cancer in Kids Study, we recruited 47 participants with anomalies and cancer, along with their biological families. Genome sequencing was performed, focusing on single-nucleotide variants, indels, and structural variants. Pathogenic or likely pathogenic variants were identified by the American College of Medical Genetics and Genomics classification.</div></div><div><h3>Results</h3><div>We identified pathogenic or likely pathogenic variants in 23.4% (11 of 47) of participants. These variants encompassed (1) 4 genes associated with both anomalies and cancer (<em>WT1</em>, <em>USP9X</em>, <em>PTPN1</em>, and <em>LZTR1</em>), (2) 2 established cancer predisposition genes (<em>TP53</em> in 2 participants and <em>PAX5</em>), and (3) 4 genes that are associated with anomalies (<em>MMUT</em>, <em>FBN1</em>, <em>COL3A1</em>, and <em>KAT6B</em>). We further investigated the role of <em>KAT6B</em> on neuroblastoma in a gene-based analysis from 409 neuroblastoma cases and 952 controls. This analysis demonstrated a significant enrichment of rare, predicted deleterious variants (<em>P</em> = .017), with odds ratios ranging from 2 to 4 based on the conditions we applied.</div></div><div><h3>Conclusion</h3><div>This study demonstrates a molecular diagnostic yield of 23.4% in participants with both anomalies and cancer. Additionally, the findings further implicate the role of <em>KAT6B</em> as a novel neuroblastoma predisposition gene.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 101901"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143162040","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":"1: Multicenter evaluation of a new AI-based karyotyping software on bone marrow specimens","authors":"Rachel D. Burnside ,&nbsp;Julie Best ,&nbsp;Lisa Spudich ,&nbsp;Amy Leftwich ,&nbsp;Marbella Ospino ,&nbsp;Ryan K. Olson ,&nbsp;Jacob Diaz ,&nbsp;Annette Mulka ,&nbsp;Yanelys Guttierez ,&nbsp;Heather Adams ,&nbsp;Kenneth Greer ,&nbsp;Julia Holmes ,&nbsp;Christy Prongay ,&nbsp;Lorraine Merant ,&nbsp;Yael Glickman ,&nbsp;Mohammad Kasom ,&nbsp;Cristina Steele ,&nbsp;Agshin F. Taghiyev ,&nbsp;Lynne S. Rosenblum","doi":"10.1016/j.gimo.2024.101918","DOIUrl":"10.1016/j.gimo.2024.101918","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 101918"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562112","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":"4: Chromosome mosaicism: A new look at an old (and perplexing) problem","authors":"Stuart Schwartz,&nbsp;Alexandra Arreola,&nbsp;Gloria Haskell,&nbsp;Andrea Penton,&nbsp;Karen Phillips,&nbsp;Jim Tepperberg,&nbsp;Inder Gadi","doi":"10.1016/j.gimo.2024.101921","DOIUrl":"10.1016/j.gimo.2024.101921","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 101921"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562210","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":"P009: Index of sustained Phe response and improvements in PKU clinical outcome assessments in patients receiving pegvaliase","authors":"Drew Levy ,&nbsp;Naomi Schwartz ,&nbsp;David Andrae ,&nbsp;Sarah Rose ,&nbsp;Hafiz Oko-osi ,&nbsp;Ogün Sazova ,&nbsp;Kristin Lindstrom","doi":"10.1016/j.gimo.2025.102853","DOIUrl":"10.1016/j.gimo.2025.102853","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 102853"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635818","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":"P006: Genetic insights from a large-scale exome sequencing study of type 1 diabetes in Ukraine","authors":"Khrystyna Shchubelka ,&nbsp;Walter Wolfsberger ,&nbsp;Taras Oleksyk","doi":"10.1016/j.gimo.2025.102850","DOIUrl":"10.1016/j.gimo.2025.102850","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 102850"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636339","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":"P040: Development and validation of a quantitative ultra-performance liquid chromatography quadrupole time-of-flight (UPLC-QTof) method for urine organic acid analysis","authors":"Yi Xiao ,&nbsp;Michael Wakefield ,&nbsp;Mari Gabra ,&nbsp;Edward Leung","doi":"10.1016/j.gimo.2025.102884","DOIUrl":"10.1016/j.gimo.2025.102884","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 102884"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636467","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":"P043: Withdrawn","authors":"","doi":"10.1016/j.gimo.2025.102887","DOIUrl":"10.1016/j.gimo.2025.102887","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 102887"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636500","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":"P032: Improving ataxia symptoms in patients with monoallelic DHDDS-CDG using nicotinamide precursor supplements","authors":"Drew Sinha ,&nbsp;Irena Muffels ,&nbsp;Ethan Perlstein ,&nbsp;Tamas Kozciz ,&nbsp;Eva Morava-Kosicz","doi":"10.1016/j.gimo.2025.102876","DOIUrl":"10.1016/j.gimo.2025.102876","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 102876"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636695","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":"P063: Anion gap metabolic acidosis of unknown etiology","authors":"Erica Gray ,&nbsp;Will Burns","doi":"10.1016/j.gimo.2025.102907","DOIUrl":"10.1016/j.gimo.2025.102907","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"3 ","pages":"Article 102907"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143636912","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}