Genetics in Medicine Open最新文献

{"title":"P015: fNIRS detects brain hemodynamics in patients with pyruvate dehydrogenase complex deficiency (PDCD)","authors":"Andrea Gropman , Melissa Greco , Kosar Khaksari","doi":"10.1016/j.gimo.2026.103506","DOIUrl":"10.1016/j.gimo.2026.103506","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103506"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394918","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":"O14: Improving detection of variant MECOM rearrangements through optical genome mapping and repurposed targeted RNA-Seq","authors":"Paige Van Haute , Holly Welfley , Chi Young Ok , Manjunath Nimmakayalu , Awdhesh Kalia , J. Bryan , L. Jeffrey Medeiros , Gokce Toruner","doi":"10.1016/j.gimo.2026.104300","DOIUrl":"10.1016/j.gimo.2026.104300","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104300"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395065","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":"P027: Volumetric MRI findings as differentiating biomarkers for juvenile-onset GM2 gangliosidoses: Tay-Sachs versus Sandhoff disease","authors":"Hera Akmal , Precilla D'Souza , Jean Johnston , Annie Tang , Maria Acosta , Cynthia Tifft","doi":"10.1016/j.gimo.2026.103518","DOIUrl":"10.1016/j.gimo.2026.103518","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103518"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395385","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":"P054: Tividenofusp alfa treatment in a male sibling pair with non-neuronopathic mucopolysaccharidosis type II","authors":"Irene Chang , Jacqeline Madden , Annie Sako , Jill Dwyer , Daniel Fertek , Adam Scheller , Sharon O'Byrne , Imanol Zubizarreta Arambarri , Peter Chin , Paul Harmatz","doi":"10.1016/j.gimo.2026.103545","DOIUrl":"10.1016/j.gimo.2026.103545","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103545"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396217","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":"O01: Clinical efficacy and safety data in adolescents treated with repinatrabit for phenylketonuria","authors":"Markey McNutt , Nicola Longo , Ania Muntau , Rani Singh , Wei Li , Tracie Davis , John Idso , Antonia Coppin-Renz , Fernanda Leal-Pardinas , Cary Harding","doi":"10.1016/j.gimo.2026.104286","DOIUrl":"10.1016/j.gimo.2026.104286","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104286"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396311","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":"P040: Pegtibatinase, an investigational enzyme replacement therapy, for the treatment of classical homocystinuria (HCU): Design of the HARMONY phase 3 study","authors":"Can Ficicioglu , Tawfeg Ben-Omran , Harvey Levy , François Maillot , Stephan vom Dahl , Cheryl Wong Po Foo , Janet Thomas","doi":"10.1016/j.gimo.2026.103531","DOIUrl":"10.1016/j.gimo.2026.103531","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103531"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396422","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":"Single vs dual genetic disease in children with congenital anomalies and solid tumors","authors":"Deborah J. Watson ,&nbsp;Amir Hossein Saeidian ,&nbsp;Xiang Wang ,&nbsp;Margaret H. Harr ,&nbsp;Yichuan Liu ,&nbsp;Yun Rose Li ,&nbsp;Shannon Terek ,&nbsp;Isabella Peixoto de Barcelos ,&nbsp;Addie Nesbitt ,&nbsp;Kenny Nguyen ,&nbsp;Xiao Chang ,&nbsp;John Connolly ,&nbsp;Cuiping Hou ,&nbsp;Isabella Slaby ,&nbsp;Fengxiang Wang ,&nbsp;James Snyder ,&nbsp;Haijun Qiu ,&nbsp;Huiqi Qu ,&nbsp;Michael E. March ,&nbsp;Xiaonan Zhao ,&nbsp;Hakon Hakonarson","doi":"10.1016/j.gimo.2026.104357","DOIUrl":"10.1016/j.gimo.2026.104357","url":null,"abstract":"<div><h3>Purpose</h3><div>Genome sequencing (GS) presents a powerful approach to uncover disease-causing genetic variants. We used GS to examine single vs dual molecular causes in some of the most complicated pediatric cases—those with both a neoplasm and a birth defect.</div></div><div><h3>Methods</h3><div>From our pediatric biobank, we selected 1463 children with a major congenital malformation, such as cleft lip/palate or internal organ defect, including 827 cases with a pediatric-onset cancer. The cohort includes nearly 40% non-White and/or multiracial individuals. We implemented GS as a first-tier diagnostic method and hypothesized that in most cases, a single disease-causing variant would explain their complex disease pictures. We developed a novel variant annotation and prioritization algorithm to provide a molecular diagnosis.</div></div><div><h3>Results</h3><div>Our algorithm uncovered 361 disease-causing single-nucleotide variants/insertion/deletions in patients with compatible phenotypes (<em>n</em> = 324/1373; 23.6%), including 207 known and 120 novel variants in 167 genes. In addition, we identified aneuploidies (<em>n</em> = 41; 3%) and disease-causing copy-number variations, including haploinsufficient regions, de novo pathogenic variants and variable degrees of mosaicism (<em>n</em> = 65, 4.7%). Likely deleterious variants were identified in 2 candidate genes, <em>GNG13</em> and <em>RTKN2</em>. Most cases had a single molecular cause for the cancer and the congenital anomaly, with notable exceptions of dual molecular causes.</div></div><div><h3>Conclusion</h3><div>In children with severe and complex phenotypes, our findings demonstrate that GS revealed causative molecular underpinnings, including novel causes. A single genetic defect may underlie phenotypes of high complexity that appear unrelated, with double molecular findings identified in the same patient on rare occasions.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104357"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358398","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":"Rates of unbalanced chromosome rearrangements associated with pericentric and paracentric inversions: Analysis of molecular chromosome results in embryo samples","authors":"Katrina Merrion,&nbsp;Jessica Adsit,&nbsp;Katherine L. Howard,&nbsp;Anjali D. Zimmer,&nbsp;Jeffrey T. Meltzer,&nbsp;Youbao Sha","doi":"10.1016/j.gimo.2026.104367","DOIUrl":"10.1016/j.gimo.2026.104367","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the outcomes of preimplantation genetic testing for structural rearrangements for individuals with pericentric or paracentric inversions undergoing in vitro fertilization.</div></div><div><h3>Methods</h3><div>This retrospective study included trophectoderm (TE) embryo biopsy samples analyzed at a single reference laboratory from 37 reproductive couples who underwent 44 in vitro fertilization cycles. TE biopsies and parental samples were genotyped using Illumina CytoSNP-12b microarrays with bioinformatic analysis to determine the parental origin of each chromosome.</div></div><div><h3>Results</h3><div>For 137 TE biopsy samples with results from 24 individuals with pericentric inversions, the frequency of deletions and duplications related to the inversion was analyzed based on the relative size of the inverted segment. We observed a rate of 5% inversion-associated deletions and duplications for samples from individuals with inversions &lt;30% of the chromosome, 3% from inversions 30% to 50% of the chromosome, and 21% from inversions &gt;50% of the chromosome. Of 43 TE biopsy samples from 7 individuals with paracentric inversions, 2% had inversion-associated deletions and duplications, and 7% had monosomy related to the parental inversion, all of which were from 1 individual.</div></div><div><h3>Conclusion</h3><div>Although previously considered to have minimal reproductive impact, we identified inversion-associated abnormalities in TE biopsy samples from individuals with paracentric and small pericentric inversions, underscoring a small but meaningful reproductive risk associated with these rearrangements.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104367"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147945172","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":"Broadening the inherited ASXL3 spectrum and unveiling molecular mechanisms through detailed genotypic-phenotypic analyses","authors":"Emily Woods,&nbsp;Nicola Holmes,&nbsp;Catherine Gooch,&nbsp;Anne-Sophie Denommé-Pichon,&nbsp;Antonio Vitobello,&nbsp;Marie Vincent,&nbsp;Efterpi Pavlidou,&nbsp;Athina Ververi,&nbsp;Virginie J.M. Verhoeven,&nbsp;Marjon A. van Slegtenhorst,&nbsp;Abhijit Dixit,&nbsp;Ajoy Sarkar,&nbsp;Meena Balasubramanian","doi":"10.1016/j.gimo.2026.104409","DOIUrl":"10.1016/j.gimo.2026.104409","url":null,"abstract":"<div><h3>Purpose</h3><div><em>ASXL3</em>-related disorder is a highly heterogeneous neurodevelopmental disorder, with increasing reports of inherited and recurrent variants indicating substantial intrafamilial phenotypic variability, as well as the possibility of interfamilial phenotypic variability.</div></div><div><h3>Methods</h3><div>In this study, we conducted a detailed genotype-phenotype review of 204 individuals from the literature, including the International ASXL3 Natural History Study (IRAS: 316055). Statistical comparisons were made between individuals with variants leading to no protein product (nonsense-mediated messenger RNA decay [NMD], <em>n</em> = 87) and those with protein-truncating variants (no-NMD, <em>n</em> = 117). Phenotypes in 2 mutational clusters, mutational cluster region 1 (MCR1) (c.1095_2237, exon 11; <em>n</em> = 66) and mutational cluster region 2 (MCR2) (c.3043_4906, exon 12; <em>n</em> = 101), were also analyzed. Clinical details of individuals with recurrent variants were compared, along with a visual representation of the genotypes associated with some rarer clinical presentations. We also describe the clinical details of families with inherited <em>ASXL3</em> variants.</div></div><div><h3>Results</h3><div>Microcephaly, sleep apnea, hyperventilation, and feeding tube use had a statistically increased prevalence in the NMD and MCR1 groups. Intellectual disability and global developmental delay were more severe in the NMD and MCR1 groups and were significant for the MCR1/MCR2 comparison (<em>P</em> = .0031 and <em>P</em> = .0183). Although autistic features were observed across all groups, the no-NMD and MCR2 cohorts had a higher proportion of individuals with formal autism diagnoses.</div></div><div><h3>Conclusion</h3><div>We describe extensive phenotypic variability through the largest-to-date series of families with inherited pathogenic or likely pathogenic <em>ASXL3</em> variants (as per the American College of Medical Genetics and Genomics classification) and a review of the clinical details of unrelated individuals with recurrent variants. The family reports emphasize the possibility of additional, yet currently unidentified, factors influencing phenotypic expression or, alternatively, may reflect uncertainty about the pathogenicity of inherited <em>ASXL3</em> variants. Our data set facilitates comprehensive molecular comparisons to elucidate genotype-phenotype correlations, overcoming the limitations of previous studies with small sample sizes or an absence of statistical analysis. These findings contribute to a deeper understanding of the underlying pathophysiological mechanisms.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104409"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581999","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":"Health-related social needs and referrals for genetic evaluation among young children","authors":"Hadley Stevens Smith,&nbsp;Kristin N. Ray,&nbsp;Lina Ghaloul Gonzalez,&nbsp;Janel Hanmer","doi":"10.1016/j.gimo.2026.104404","DOIUrl":"10.1016/j.gimo.2026.104404","url":null,"abstract":"<div><div>Health-related social needs (HRSNs) may impact the receipt of genetic services, but the mechanisms are not well established. We aimed to evaluate the relationship between pediatric patients’ HRSNs and referrals for genetic evaluation. We analyzed HRSN survey data collected during clinic visits across 47 primary care offices for children &lt;3 years of age. Using hazard ratios adjusted (aHRs) for child characteristics, we evaluated the relative likelihood of referral for genetic evaluation based on categories of HRSN. The sample included 42,390 children, 470 of whom received a referral for genetic evaluation. Children who screened positive for any HRSN (<em>n</em> = 235/15,019) were more likely to be referred than children who did not screen positive (<em>n</em> = 235/27,371; aHR = 1.29, <em>P</em> = .009). Children were more likely to receive referrals if they were insured by Medicaid rather than commercial insurance (aHR = 2.32, <em>P</em> &lt; .0001), and if they received care in academic primary care clinics rather than community ones (aHR = 2.52, <em>P</em> &lt; .0001). Holding child characteristics and other HRSNs constant, parent-reported financial stress was associated with a higher likelihood of referral (aHR = 1.38, <em>P</em> = .004). Child race and ethnicity were not significant predictors of referral in adjusted analyses. Children in our sample with any HRSN were more likely to receive a referral for genetic evaluation, which is a key step toward genetic diagnosis. Our findings highlight the need to better understand the relationship between HRSNs and genetic referrals and services.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104404"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148735614","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}