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P048: Three year safety experience in children treated with govorestat for classic galactosemia P048：用govorestat治疗经典半乳糖血症儿童3年的安全性经验

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.102892

Evan Bailey , Riccardo Perfetti , Shoshana Shendelman

引用次数: 0

P050: Integrating metabolic, genetic, and demographic data for enhanced newborn screening P050：整合代谢、遗传和人口统计数据，加强新生儿筛查

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.102894

Curt Scharfe , Yuhan Xie , Gang Peng , Laura Forero , Gregory Enns , Hongyu Zhao , Tina Cowan

引用次数: 0

O01: Efficacy and safety outcomes of JNT-517, a first-in-class SLC6A19 inhibitor, in adults with phenylketonuria: A randomized study 01：一项随机研究：JNT-517（一种SLC6A19抑制剂）治疗成人苯丙酮尿症的疗效和安全性

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.101964

Cary Harding , Nicola Longo , Andreu Viader , Toby Vaughn , Fernanda Leal-Pardinas , Elaina Jurecki , Markey McNutt II , Ania Muntau , Rani Singh , Joel Barrish , George Vratsanos , Haoling Weng , John Throup

引用次数: 0

P082: Expanding clinical spectrums in carbamoyl phosphate synthetase I deficiency: A case series of four patients - a tertiary institution’s experience P082：扩大磷酸氨基甲酰合成酶I缺乏症的临床范围：一个由四名患者组成的病例系列-一个高等教育机构的经验

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.102926

Vittoria Rossi , Brittany Hoyle , Kim Ng , Ivy Elvin , Nicole Engelhardt

引用次数: 0

P028: Population-specific structural variation linked to metabolic diseases in people of Pacific ancestry P028：太平洋血统人群中与代谢性疾病相关的群体特异性结构变异

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.102872

Connor Littlefield , Jose Lazaro-Guevara , Devorah Stucki , Michael Lansford , Melissa Pezzolesi , Emma Taylor , Jacob Taloa , Kime Lao , Justina Tavana , William Holland , Kalani Raphael , Marcus Pezzolesi

引用次数: 0

Enhanced detection and characterization of germline structural variants in cancer predisposition genes via genome sequencing 通过基因组测序增强癌症易感基因种系结构变异的检测和表征

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.103459

Parisa K. Kargaran , Qiliang Ding , Lauren A. Choate , Heidi L. Sellers , Mariam I. Stein , Belle A. Moyers , Shubham Basu , Pratyush P. Tandale , Rohit Setlem , Megan F. Bishop , Megan A. Holdren , Rhianna M. Urban , Sounak Gupta , Wei Shen

Purpose

Germline pathogenic variants in cancer predisposition genes are found in approximately 10% of all cancer cases. Although multigene panel testing is the current first-tier approach for detecting variants in these genes, it has limitations in identifying and characterizing copy-number variants and other structural variants (SVs). Genome sequencing (GS) provides a more uniform coverage throughout the genome, thereby offering a more comprehensive method for copy-number variant and SV detection; however, its diagnostic utility in genetic testing for cancer predisposition remains underexplored.

Methods

In this study, we performed GS on 33 patients with previously identified germline SVs in cancer predisposition genes, including 25 deletions, 7 duplications, and 1 mobile element insertion.

Results

Using 2 SV callers in the DRAGEN pipeline, GS achieved 100% sensitivity in detecting these SVs. Moreover, GS revealed additional insights not available through previous clinical testing in 9 (27%) cases, including identifying a complex SV, clarifying structural configuration of intragenic duplications, and refining breakpoints at base-pair resolution.

Conclusion

Taken together, our findings support the utility of GS as the sequencing backbone for germline genetic testing of cancer predisposition genes with improved detection, characterization, and clinical interpretation of SVs.

目的：癌症易感基因的种系致病性变异在所有癌症病例中约占10%。虽然多基因面板检测是目前检测这些基因变异的第一层方法，但它在识别和表征拷贝数变异和其他结构变异（sv）方面存在局限性。基因组测序（GS）在整个基因组中提供了更均匀的覆盖范围，从而为拷贝数变异和SV检测提供了更全面的方法；然而，它在癌症易感性基因检测中的诊断效用仍未得到充分探索。方法在本研究中，我们对33例癌症易感基因中已鉴定的种系SVs患者进行了GS检测，包括25个缺失、7个重复和1个移动元件插入。结果在DRAGEN管道中使用2个SV调用者，GS对SV的检测灵敏度达到100%。此外，GS在9例（27%）病例中揭示了以前临床试验无法获得的其他见解，包括识别复杂的SV，阐明基因内重复的结构配置，以及在碱基对分辨率上改进断点。综上所述，我们的研究结果支持GS作为癌症易感基因种系基因检测的测序骨干，可以改进SVs的检测、表征和临床解释。

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引用次数: 0

Assessing completeness of cancer family history in EHRs using genetically defined kinships: A cross-sectional study 利用基因定义的亲属关系评估电子病历中癌症家族史的完整性：一项横断面研究

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.103450

Daniel Kiser , Gai Elhanan , Karen A. Schlauch , Robert Read , Joseph J. Grzymski

Purpose

Family history (FHx) is the most widely available tool for reducing mortality and morbidity caused by heritable diseases. However, FHx may be inadequately documented. Our objective was to assess the rate at which cancers in patient relatives are documented as FHx in electronic health records (EHRs).

Methods

Our primary analysis included 903 Healthy Nevada Project participants who had cancer-diagnosed patient relatives removed by ≤2 degrees in a kinship analysis. The rate of successful EHR documentation of relatives’ cancer type was quantified using generalized estimating equations.

Results

The population-average rate of cancer FHx documentation in the EHR was 45.2% (95% confidence interval [CI]: 42.0%-48.4%). The odds ratio (OR) for successful documentation was 0.39 (95% CI: 0.24-0.64) for patients >69 years old versus patients <30 years old. Additionally, FHx documentation increased with years since a relative’s cancer diagnosis, with an OR of 2.19 (95% CI: 1.57-3.06) for patients with ≥10 years since their relative’s diagnosis versus <5 years. Compared with females, males were less likely to document female-specific cancers (OR 0.31 [95% CI: 0.19-0.49]) but more likely to document male-specific cancers (OR 2.42 [95% CI: 1.16-5.04]). In a secondary analysis of 83 patients with variants in BRCA1 or BRCA2, 34 (41%) met familial risk criteria based on their EHRs; however, an additional 6 (7%) would have met criteria if cancers in known relatives had been documented.

Conclusion

More than half of cancers affecting patient relatives were not documented as FHx in patient EHRs. This suggests that familial risk is underestimated, likely resulting in missed opportunities to reduce cancer mortality and morbidity.

目的家族史（FHx）是降低遗传性疾病引起的死亡率和发病率最广泛使用的工具。然而，FHx可能没有充分的文件记录。我们的目的是评估患者亲属的癌症在电子健康记录（EHRs）中被记录为FHx的比率。方法我们的主要分析包括903名健康内华达项目参与者，他们的癌症诊断患者亲属在亲属关系分析中被剔除≤2度。采用广义估计方程对亲属癌症类型的电子病历记录成功率进行量化。结果EHR中FHx记录的人群平均率为45.2%（95%可信区间[CI]: 42.0% ~ 48.4%）。对于69岁的患者和30岁的患者，成功记录的优势比（OR）为0.39 （95% CI: 0.24-0.64）。此外，亲属癌症诊断后FHx记录随着时间的增加而增加，亲属诊断后≥10年的患者与5年的患者的OR为2.19 （95% CI: 1.57-3.06）。与女性相比，男性较少记录女性特异性癌症（OR为0.31 [95% CI: 0.19-0.49]），但更容易记录男性特异性癌症（OR为2.42 [95% CI: 1.16-5.04]）。在对83例BRCA1或BRCA2变异患者的二次分析中，34例（41%）符合基于其电子病历的家族风险标准；然而，如果已知亲属中有癌症记录，则另有6人（7%）符合标准。结论患者电子病历中超过半数影响患者亲属的癌症未记录为FHx。这表明家族性风险被低估了，可能导致错过了降低癌症死亡率和发病率的机会。

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引用次数: 0

Perspectives from the 2024 International Consortium for Spinal Genetics, Development and Disease (ICSGDD) 2024年国际脊柱遗传、发育和疾病协会（ICSGDD）展望

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2025.103466

Nan Wu , Nancy Hadley-Miller , Ryan Gray , Stevana Schauer , Gregory Redding , Tian Cheng , Zefu Chen , Jianle Yang , Ronen Blecher , Paul Gerdhem , Carol A. Wise

引用次数: 0

35: A rare mechanism of Russell-Silver syndrome acquired from a maternally derived unbalanced translocation, t(X;11) 35：一种罕见的罗素-希尔弗综合征机制，由母源性不平衡易位（t(X;11)

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2024.101952

Rebecca B. Smith , Ashwini Yenamandra , Meng-Chang Hsiao , Yingda Wang , Sophia D. Stewart , Rory Tinker , Neena Agrawal

引用次数: 0

30: FUS rearrangements/fusions by FISH and RNA-based gene fusion assays in sarcomas 30：用FISH和基于rna的基因融合检测肉瘤中的FUS重排/融合

Genetics in Medicine Open

Pub Date : 2025-01-01 DOI: 10.1016/j.gimo.2024.101947

Candice Ament

引用次数: 0

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