Genetics in Medicine Open最新文献_第8页

Evaluating and monitoring liver disease severity in glycogen storage disease type IX: Performance of novel and established clinical scores 评估和监测糖原储存病IX型肝病严重程度：新的和已建立的临床评分的表现

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2025-09-10 DOI: 10.1016/j.gimo.2025.103455

Anna Paschall , Rebecca L. Koch , Alisha M. Mavis , Leticia S. Flores , Rajan T. Gupta , William R. Jeck , Carolina Fischinger Moura de Souza , Bibiana Mello de Oliveira , Vikrant Sood , Seema Alam , Gilda Porta , Sheela Nampoothiri , Neerja Gupta , Jose Abdenur , Aruna Rikhi , Jessica Doxey , Andrew J. Muir , Priya S. Kishnani

{"title":"Evaluating and monitoring liver disease severity in glycogen storage disease type IX: Performance of novel and established clinical scores","authors":"Anna Paschall , Rebecca L. Koch , Alisha M. Mavis , Leticia S. Flores , Rajan T. Gupta , William R. Jeck , Carolina Fischinger Moura de Souza , Bibiana Mello de Oliveira , Vikrant Sood , Seema Alam , Gilda Porta , Sheela Nampoothiri , Neerja Gupta , Jose Abdenur , Aruna Rikhi , Jessica Doxey , Andrew J. Muir , Priya S. Kishnani","doi":"10.1016/j.gimo.2025.103455","DOIUrl":"10.1016/j.gimo.2025.103455","url":null,"abstract":"<div><h3>Purpose</h3><div>Hepatic glycogen storage disease type IX (GSD IX) results from a deficiency of phosphorylase kinase. A noninvasive method of monitoring liver disease severity in this population is unavailable and liver biopsy remains the gold standard for classifying disease severity, particularly for liver fibrosis.</div></div><div><h3>Methods</h3><div>We proposed 2 novel hepatic GSD IX-specific liver disease severity scoring systems: one that incorporated laboratory parameters (“novel lab-only score”) and one that incorporated laboratory, abdominal imaging, and growth parameters (“novel comprehensive score”). We compared their performance with established scoring systems used for other liver diseases and liver biopsy to determine concordance.</div></div><div><h3>Results</h3><div>Liver disease severity was assessed in 56 pediatric participants with hepatic GSD IX. The novel lab-only and comprehensive scores correctly differentiated between mild and severe liver disease in 72.4% and 66.7% of participants, respectively. The Pediatric Non-Alcoholic Fatty Liver Disease Fibrosis Score demonstrated the highest accuracy in liver disease severity classification, correctly differentiating between mild and severe liver disease in 82.4% of participants.</div></div><div><h3>Conclusion</h3><div>Hepatic GSD IX requires longitudinal monitoring and liver disease severity prediction scores may be useful clinical tools to noninvasively grade the severity of liver disease. Liver biopsy remains an important part of clinical management to understand the extent of liver disease.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103455"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147945170","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}

引用次数: 0

ACMG Medical Directors’ Special Interest Group survey: Current challenges for medical genetics clinics ACMG医学主任特别兴趣小组调查：医学遗传学诊所当前面临的挑战

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-03-25 DOI: 10.1016/j.gimo.2026.104392

Mark Dulchavsky , Catherine E. Keegan , Nathaniel H. Robin , Chad Haldeman-Englert , Shweta U. Dhar , Fuki M. Hisama

{"title":"ACMG Medical Directors’ Special Interest Group survey: Current challenges for medical genetics clinics","authors":"Mark Dulchavsky , Catherine E. Keegan , Nathaniel H. Robin , Chad Haldeman-Englert , Shweta U. Dhar , Fuki M. Hisama","doi":"10.1016/j.gimo.2026.104392","DOIUrl":"10.1016/j.gimo.2026.104392","url":null,"abstract":"<div><h3>Purpose</h3><div>The American College of Medical Genetics and Genomics Medical Directors’ Special Interest Group (SIG) began in 2021 as a forum for directors of medical genetics clinical groups to share questions, concerns, current practices, and solutions regarding clinical operations. We report on the first 4 years of the SIG—its membership growth and SIG activities. We also present quantitative and qualitative results of a nationwide survey of 66 SIG members addressing recurrent questions from members regarding: wait times, volume of referrals, clinical workload expectations, and independent practice of genetic counselors (GCs) and advanced practice providers.</div></div><div><h3>Methods</h3><div>Cross-sectional survey of American College of Medical Genetics and Genomics Medical Directors’ Special Interest Group members.</div></div><div><h3>Results</h3><div>We found that clinical full-time equivalents expectations are higher for medical geneticists than advanced practice providers, which were higher than for GCs. In 76% (44/58) of programs, GCs see patients independently, although many require a medical geneticist cosignature for orders, and only 51% (30/59) of programs report that GCs can bill independently. Clinic wait times for routine visits vary by subspecialty; the longest wait times are for general pediatric and adult genetic services (49% [21/43] of visits had wait times > 6 months), whereas wait times > 6 months were reported for only 26% (9/34) of cancer genetic visits, 7% (3/43) of biochemical genetics visits, and 0% (0/26) of prenatal visits. Urgent visit wait times were generally less than 2 weeks.</div></div><div><h3>Conclusion</h3><div>Wait times for clinical genetics appointments continue to increase compared with surveys from previous years. Medical genetics clinics are comprised of a heterogeneous workforce, and strategies to reduce wait times are similarly diverse.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104392"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147706347","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}

引用次数: 0

Reclassification of missense variant pathogenicity using ClinGen recommendations for recalibrated PP3/BP4 in silico predictor score thresholds 使用ClinGen建议重新校准PP3/BP4在计算机预测评分阈值中的错义变异致病性的重新分类

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-03-23 DOI: 10.1016/j.gimo.2026.104395

Joseph B. Dubé , Sean Kim , Lynette Lau , Ted Higginbotham , Christian R. Marshall , Rebekah K. Jobling

{"title":"Reclassification of missense variant pathogenicity using ClinGen recommendations for recalibrated PP3/BP4 in silico predictor score thresholds","authors":"Joseph B. Dubé , Sean Kim , Lynette Lau , Ted Higginbotham , Christian R. Marshall , Rebekah K. Jobling","doi":"10.1016/j.gimo.2026.104395","DOIUrl":"10.1016/j.gimo.2026.104395","url":null,"abstract":"<div><h3>Purpose</h3><div>To estimate the effect of ClinGen-calibrated variant effect predictor (VEP) score thresholds on clinically-reported missense variants of uncertain significance (VUS) reclassification using 2015 American College of Medical Genetics/Association for Molecular Pathology variant classification guidelines.</div></div><div><h3>Methods</h3><div>Missense VUS were reported from clinically indicated genome-wide sequencing or targeted multigene panel testing. Variants were reclassified after integrating select recalibrated VEP pathogenicity scores within the existing 2015 American College of Medical Genetics/Association for Molecular Pathology guidelines. VEPs include VARITY, AlphaMissense, ESM1b, BayesDel, VEST4, REVEL, PolyPhen-2, and SIFT.</div></div><div><h3>Results</h3><div>Overall median percentage of reclassified missense VUS was 5%. VARITY demonstrated the highest median percent reclassification of missense VUS at approximately 7%. VUS reclassifications from 7 of 8 VEPs demonstrated complete agreement when compared with VUS reclassifications from all other VEPs, except for VARITY which demonstrated a mean percentage agreement of 91%. ESM1b and SIFT demonstrated significantly higher proportions of VUS reclassifications to likely benign compared with likely pathogenic. There was no association between VUS reclassification and autosomal mode of inheritance; however, SIFT and VEST4 demonstrated significantly higher reclassifications of VUS from autosomal dominant genes versus autosomal recessive genes.</div></div><div><h3>Conclusion</h3><div>Recalibrated VEP pathogenicity score thresholds modestly affect missense VUS reclassification. The included VEPs largely demonstrated equal VUS reclassifications to likely pathogenic or likely benign with near complete agreement in VUS reclassification between the included VEPs.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104395"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147740285","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}

引用次数: 0

Rare and resilient: Longer-term experiences of families after genetic evaluation in the neonatal intensive care unit 罕见和弹性：新生儿重症监护室遗传评估后家庭的长期经验

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2025-12-20 DOI: 10.1016/j.gimo.2025.103490

Siwaar Abouhala , Maya C. del Rosario , Ingrid A. Holm , Monica H. Wojcik

{"title":"Rare and resilient: Longer-term experiences of families after genetic evaluation in the neonatal intensive care unit","authors":"Siwaar Abouhala , Maya C. del Rosario , Ingrid A. Holm , Monica H. Wojcik","doi":"10.1016/j.gimo.2025.103490","DOIUrl":"10.1016/j.gimo.2025.103490","url":null,"abstract":"<div><h3>Purpose</h3><div>Many rare genetic conditions manifest soon after birth and result in admission to the Neonatal Intensive Care Unit (NICU), where prior research suggests that parents experience high levels of stress and uncertainty. However, further insight into parent-reported, longer-term outcomes for these infants and their families is needed.</div></div><div><h3>Methods</h3><div>We undertook a qualitative analysis of parent-reported experiences with genomic care over the course of their NICU admission and beyond, after an initial quantitative study of 110 families who received genetic evaluation in the NICU, in a mixed-methods approach. Twenty families participated in individual semistructured interviews eliciting the impact of the NICU experience and genetic diagnostic odyssey on the infant and family.</div></div><div><h3>Results</h3><div>We identified 4 main themes: (1) Rare Disease as “Culture Shock,” (2) Parental Trauma and Stressors, (3) Family Resiliency, and (4) Hospital System Recommendations. Early, rapid, and broad genomic testing was appreciated by parents, although additional genomic- and nongenomic supports after NICU discharge were desired. Stressors in the NICU related to uncertainty and critical illness occurred independent of genetic testing applications or results. Parents reported adapting their expectations regarding the benefits of a genetic diagnosis over time, ultimately focusing on day-to-day care and finding pride in medical and social resilience.</div></div><div><h3>Conclusion</h3><div>The NICU experience, particularly for infants with rare conditions, has long-lasting impact on the family. Enhanced attention to longitudinal supports from NICU to home may be beneficial for families undergoing genetic diagnostic odysseys.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 103490"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078111","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}

引用次数: 0

Rapid functional RNA Analysis via amniocyte transdifferentiation resolves prenatal variant ambiguity in fetal akinesia syndrome 通过羊膜细胞转分化的快速功能RNA分析解决胎儿运动障碍综合征的产前变异歧义

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-03-23 DOI: 10.1016/j.gimo.2026.104393

Yiming Qi , Jiahui Sun , Wei He , Jing Wu , Aihua Yin

引用次数: 0

Genome sequencing reveals the prevalence of Fabry disease–causing variants in Japan: Evidence from the Tohoku Medical Megabank 基因组测序揭示了法布里病致病变异在日本的流行：来自东北医疗大银行的证据

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-08-07 DOI: 10.1016/j.gimo.2026.104490

Kai Susukita, Kotaro Nochioka, Masato Takase, Saori Yamamoto, Kazuki Kumada, Hideaki Suzuki, Kinuko Ohneda, Kenichi Noguchi, Yoko Izumi, Soichi Ogishima, Naoki Nakaya, Yoshikatsu Eto, Atsushi Hozawa, Satoshi Yasuda

{"title":"Genome sequencing reveals the prevalence of Fabry disease–causing variants in Japan: Evidence from the Tohoku Medical Megabank","authors":"Kai Susukita, Kotaro Nochioka, Masato Takase, Saori Yamamoto, Kazuki Kumada, Hideaki Suzuki, Kinuko Ohneda, Kenichi Noguchi, Yoko Izumi, Soichi Ogishima, Naoki Nakaya, Yoshikatsu Eto, Atsushi Hozawa, Satoshi Yasuda","doi":"10.1016/j.gimo.2026.104490","DOIUrl":"10.1016/j.gimo.2026.104490","url":null,"abstract":"<div><h3>Background</h3><div>Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficient α-galactosidase A activity and characterized by multisystem involvement. Although considered rare, with reported prevalence ranging from 1 in 40,000 to 1 in 140,000, its true frequency in the general population remains uncertain. We aimed to determine the prevalence of FD-causing variants in a community-based cohort from the Tohoku Medical Megabank, Japan.</div></div><div><h3>Methods</h3><div>Genome sequencing was performed in 68,615 individuals. Variant pathogenicity was classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Baseline demographics, serum α-galactosidase A (GLA) activity, plasma globotriaosylsphingosine, and self-reported health data were assessed.</div></div><div><h3>Results</h3><div>Pathogenic GLA variants were identified in 4 individuals and a likely pathogenic variant in 1 individual (mean age 49.3 ± 15.9 years); all were female, corresponding to a prevalence of 1 in 13,723. All pathogenic variants were c.902G>A, associated with the cardiac phenotype, whereas the likely pathogenic variant was c.1076T>C. Mean plasma GLA activity was 5.64 ± 1.73 mmol/hr/mL in pathogenic variant carriers and 8.36 mmol/hr/mL in the likely pathogenic carrier. Plasma globotriaosylsphingosine levels were 3.7 ± 0.79 ng/mL and 0.96 ng/mL, respectively.</div></div><div><h3>Conclusion</h3><div>Population based genome sequencing data suggest a higher prevalence of FD-causing variants in Japan than previously reported, highlighting potential underdiagnosis of late-onset FD in women.</div></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":"4 ","pages":"Article 104490"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148995380","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}

引用次数: 0

P002: Exploring the role of cardiolipin metabolism in the brain through the lens of Barth syndrome and cardiolipin synthase deficiency* P002：从Barth综合征和心磷脂合成酶缺乏症的角度探讨脑内心磷脂代谢的作用*

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-03-05 DOI: 10.1016/j.gimo.2026.103493

Kodi Harris , Olivia Sniezek-Carney , Gregory Newby , Kathryn Chatfield , Genevieve Sparagna , Anne Hamacher-Brady , Hilary Vernon

引用次数: 0

P035: A pilot study investigating the use and monitoring of LNAA P035：一项调查LNAA使用和监测的试点研究

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-03-05 DOI: 10.1016/j.gimo.2026.103526

Jessica Bolen , Paige Roberts , Kate Richardson , Laura Farach , Hope Northrup

引用次数: 0

O07: Inhibiting Wnt/β-catenin-mTOR signaling enhances porphyrin clearance in porphyrias with hepatic involvement [07]抑制Wnt/β-catenin-mTOR信号传导可增强肝脏病变卟啉症的卟啉清除

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-03-05 DOI: 10.1016/j.gimo.2026.104292

Kari Nejak-Bowen , Oluwashanu Balogun

引用次数: 0

P066: Integrating tumor-normal testing to clarify the significance of adult-onset cancer predisposition genes in pediatric cancer patients* P066：整合肿瘤-正常检测，阐明儿童癌症成人发病易感基因的意义*

Genetics in Medicine Open Pub Date : 2026-01-01 Epub Date: 2026-03-05 DOI: 10.1016/j.gimo.2026.104303

Mohammad Eldomery , Jamie Maciaszek , Taylor Cain , Victor Pastor Loyola , Patrick Blackburn , Mark Wilkinson , Maria Cardenas , Selene Koo , Lu Wang , Kim Nichols , Jeffery Klco

引用次数: 0