Genetics in Medicine Open最新文献

{"title":"The challenges and opportunities of offering and integrating training in clinical molecular genetics and clinical cytogenetics: a survey of LGG Fellowship Program Directors","authors":"Joshua L. Deignan, Vimla Aggarwal, Allen E. Bale, Daniel B. Bellissimo, Jessica K. Booker, Yang Cao, Kristy R. Crooks, Kristen L. Deak, Daniela del Gaudio, Birgit Funke, N. Hoppman, Vanessa L. Horner, Robert B. Hufnagel, Colleen Jackson-Cook, Prasad Koduru, Marco L. Leung, Shibo Li, Pengfei Liu, Minjie Luo, Rong Mao, Heather Mason-Suares, Fady M. Mikhail, Stephen R. Moore, Rizwan Naeem, Laura M. Pollard, Elena A. Repnikova, Lina Shao, Brandon M. Shaw, Shashirekha Shetty, Teresa A. Smolarek, Elizabeth Spiteri, Jessica Van Ziffle, Gail H. Vance, Cindy L. Vnencak-Jones, Eli S. Williams","doi":"10.1016/j.gimo.2024.101820","DOIUrl":"https://doi.org/10.1016/j.gimo.2024.101820","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139879547","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":"Next-generation variant exon screening: Moving forward in routine genetic disease investigations","authors":"Conghui Wang ,&nbsp;Panlai Shi ,&nbsp;Hongbin Liang ,&nbsp;David S. Cram ,&nbsp;Donald A. Leigh ,&nbsp;Xiangdong Kong","doi":"10.1016/j.gimo.2024.101816","DOIUrl":"https://doi.org/10.1016/j.gimo.2024.101816","url":null,"abstract":"<div><h3>Purpose</h3><p>Patients with genetic diseases often seek testing to reach a firm diagnosis. Based on clinical phenotypes, exome sequencing for small-nucleotide variations or array-based methods for copy-number variations (CNVs) are commonly offered to identify the underlying causative genetic variants. In this study, we investigated whether data from a standard ES test could be used to additionally identify pathogenic CNVs and increase diagnostic yield.</p></div><div><h3>Methods</h3><p>Prospectively, 134 patients presenting with a skin condition suspected of being genetic in origin were offered the next-generation variant exon screening (ngVES) test. Sequencing data were analyzed for both single-nucleotide variants and CNVs using established algorithms.</p></div><div><h3>Results</h3><p>The positive detection rate for skin diseases using ngVES was 66% (88/134) with the most common diagnoses being neurofibromatosis type1 (<em>n</em> = 48) and tuberous sclerosis type2 (<em>n</em> = 12). The diagnostic increased yield from 58% to 66% was the result of additional detection of pathogenic CNVs. Each of the 9 CNVs were verified by independent genetic tests.</p></div><div><h3>Conclusion</h3><p>The advances in the ngVES bioinformatics pipeline are proofs of concept, which improved identification of genetic variants associated with skin disease. Simultaneous single-nucleotide variants/INDEL and CNV detection by this approach demonstrates ngVES potential as a first-tier screen for any suspected genetic disease.</p></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424009622/pdfft?md5=f2e67b15763bc281fc0aac895e1ac049&pid=1-s2.0-S2949774424009622-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140134187","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":"The impact of the Turkish population variome on the genomic architecture of rare disease traits","authors":"Zeynep Coban-Akdemir ,&nbsp;Xiaofei Song ,&nbsp;Francisco C. Ceballos ,&nbsp;Davut Pehlivan ,&nbsp;Ender Karaca ,&nbsp;Yavuz Bayram ,&nbsp;Tadahiro Mitani ,&nbsp;Tomasz Gambin ,&nbsp;Tugce Bozkurt-Yozgatli ,&nbsp;Shalini N. Jhangiani ,&nbsp;Donna M. Muzny ,&nbsp;Richard A. Lewis ,&nbsp;Pengfei Liu ,&nbsp;Eric Boerwinkle ,&nbsp;Ada Hamosh ,&nbsp;Richard A. Gibbs ,&nbsp;V. Reid Sutton ,&nbsp;Nara Sobreira ,&nbsp;Claudia M.B. Carvalho ,&nbsp;Chad A. Shaw ,&nbsp;James R. Lupski","doi":"10.1016/j.gimo.2024.101830","DOIUrl":"https://doi.org/10.1016/j.gimo.2024.101830","url":null,"abstract":"<div><h3>Purpose</h3><p>The variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated for insights on the genomic architecture of disease.</p></div><div><h3>Methods</h3><p>We generated and analyzed a database of variants derived from exome sequencing data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits and 643 unaffected relatives.</p></div><div><h3>Results</h3><p>Using uniform manifold approximation and projection, we showed that the TK genomes are more similar to those of Europeans and consist of 2 main subpopulations: clusters 1 and 2 (<em>N</em> = 235 and 1181, respectively), which differ in admixture proportion and variome (<span>https://turkishvariomedb.shinyapps.io/tvdb/</span><svg><path></path></svg>). Furthermore, the higher inbreeding coefficient values observed in the TK affected compared with unaffected individuals correlated with a larger median span of long-sized (&gt;2.64 Mb) runs of homozygosity (ROH) regions (<em>P</em> value = 2.09e-18). We show that long-sized ROHs are more likely to be formed on recently configured haplotypes enriched for rare homozygous deleterious variants in the TK affected compared with TK unaffected individuals (<em>P</em> value = 3.35e-11). Analysis of genotype-phenotype correlations reveals that genes with rare homozygous deleterious variants in long-sized ROHs provide the most comprehensive set of molecular diagnoses for the observed disease traits with a systematic quantitative analysis of Human Phenotype Ontology terms.</p></div><div><h3>Conclusion</h3><p>Our findings support the notion that novel rare variants on newly configured haplotypes arising within the recent past generations of a family or clan contribute significantly to recessive disease traits in the TK population.</p></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424009762/pdfft?md5=da4ee623adf418d755f779d1f6d2fa94&pid=1-s2.0-S2949774424009762-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140163773","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":"P020: Recommendations from the ClinGen Peroxisomal Variant Curation Expert Panel for variant classification in ABCD1","authors":"Shruthi Mohan ,&nbsp;Irene De Biase ,&nbsp;Tatiana Yuzyuk ,&nbsp;Alexa Dickson ,&nbsp;Tiziano Pramparo ,&nbsp;Stephanie Francis ,&nbsp;Meredith Weaver ,&nbsp;Raquel Fernandez ,&nbsp;Sharon Suchy ,&nbsp;Ann Moser ,&nbsp;Rong Mao ,&nbsp;Nancy Braverman","doi":"10.1016/j.gimo.2024.100897","DOIUrl":"https://doi.org/10.1016/j.gimo.2024.100897","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424000438/pdfft?md5=fbcbe72bc1fb7e9764155de82487f731&pid=1-s2.0-S2949774424000438-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061771","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":"P001: Outcomes In 14 live births resulting from pegvaliase-treated pregnancies in females with PKU*","authors":"Caide Bier ,&nbsp;Kaelin Dickey ,&nbsp;Hans Andersson ,&nbsp;Markey McNutt ,&nbsp;Danielle Vice ,&nbsp;Erin Cooney ,&nbsp;Megan Morand ,&nbsp;Joseph Ray ,&nbsp;Rebecca Sponberg ,&nbsp;Richard Chang ,&nbsp;Monica Boyer ,&nbsp;Brittan Bibb ,&nbsp;Angela Crutcher ,&nbsp;Melissa Lah ,&nbsp;Laura Davis-Keppen ,&nbsp;Cindy Matthes","doi":"10.1016/j.gimo.2024.100878","DOIUrl":"https://doi.org/10.1016/j.gimo.2024.100878","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424000244/pdfft?md5=859df8c3fae42169ba5cf4303aec2fd1&pid=1-s2.0-S2949774424000244-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061946","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":"P010: Genetic testing is incompletely sensitive for treatable inherited metabolic disorders","authors":"Sarah Bick ,&nbsp;Monica Wojcik ,&nbsp;Robert Green ,&nbsp;Nina Gold","doi":"10.1016/j.gimo.2024.100887","DOIUrl":"https://doi.org/10.1016/j.gimo.2024.100887","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424000335/pdfft?md5=26acbb0479e88ed27756207116891da2&pid=1-s2.0-S2949774424000335-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061949","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":"P065: The clinical utility of plasma circulating tumor DNA in the diagnosis and disease surveillance in non-DLBCL non-Hodgkin’s lymphomas*","authors":"Minyi Zhu ,&nbsp;Xiaotian Zhao ,&nbsp;Yao Xiao ,&nbsp;Jiaohui Pang ,&nbsp;Liuqing Zhu ,&nbsp;Ruoying Yu ,&nbsp;Qiuxiang Ou","doi":"10.1016/j.gimo.2024.100947","DOIUrl":"https://doi.org/10.1016/j.gimo.2024.100947","url":null,"abstract":"","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424000931/pdfft?md5=bcca1fe076e412db8093ac99dc3c2568&pid=1-s2.0-S2949774424000931-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140062654","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":"Blind to the perils of pursuing food: Behaviors of individuals with Smith-Magenis Syndrome","authors":"","doi":"10.1016/j.gimo.2024.101857","DOIUrl":"10.1016/j.gimo.2024.101857","url":null,"abstract":"<div><h3>Purpose</h3><p>Discrepancies exist between the need to lock food away and satiety scores in the Smith-Magenis syndrome (SMS) population. This study sought to uncover food-related behaviors within this unique group of individuals.</p></div><div><h3>Methods</h3><p>Caregivers (<em>N</em> = 24) representing 21 individuals with SMS, recruited from the Parents and Researchers Interested in SMS national meeting and social media platforms, participated in semistructured interviews. Interviews were digitally recorded, transcribed verbatim, coded, and analyzed using hybrid thematic analysis.</p></div><div><h3>Results</h3><p>This study identified a global theme of “Blind to the perils while pursuing their goals,” supported by 5 organizing themes: (1) Biology-impacting behaviors, (2) Need for personalized strategies, (3) Controlling food experiences, (4) Need for parents to orchestrate life, and (5) Surprising resourcefulness. Subthemes within these organizing themes highlighted that individuals with SMS have unique food-related behaviors and often fixate on certain types of foods. Their constant obsession with food for many of them is driven by hunger, obsessive characteristics, a need for autonomy, and a need for fairness. Caregivers must put multiple guardrails in place and remain constantly vigilant to prevent overeating in these individuals.</p></div><div><h3>Conclusion</h3><p>Individuals with SMS often perseverate on food and display unique food-related behaviors. Treating obesity in this population is likely to be ineffective without multicomponent, individualized strategies. Additionally, research in this population will likely require targeted instruments for the SMS population to more clearly define the underlying etiologies and to track changes over time in therapeutic trials.</p></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424010033/pdfft?md5=504372893ffa66c41d6839c08769a058&pid=1-s2.0-S2949774424010033-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407373","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":"A combination of long- and short-read genomics reveals frequent p-arm breakpoints within chromosome 21 complex genomic rearrangements","authors":"","doi":"10.1016/j.gimo.2024.101863","DOIUrl":"10.1016/j.gimo.2024.101863","url":null,"abstract":"<div><h3>Purpose</h3><p>Although chromosome 21 is the smallest human chromosome, it is highly relevant in the pathogenicity of both cancer and congenital diseases, including Alzheimer disease and trisomy 21 (Down syndrome). In addition, cases with rare structural variants (SVs) of chromosome 21 have been reported. These events vary in size and include large chromosomal events, such as ring chromosomes and small partial aneuploidies. The p-arm of the acrocentric chromosome 21 was devoid of reference genomic sequence in GRCh37 and GRCh38, which hampered our ability to solve genomic rearrangements and find the mechanism of formation of disease-causing SVs. We hypothesize that conserved satellite structures and segmental duplications located on the p-arm play an important role in the formation of complex SVs involving chromosome 21.</p></div><div><h3>Methods</h3><p>Three cases with complex chromosome 21 rearrangements were studied with a combination of short-read and long-read genome sequencing, as well as optical genome mapping. The data were aligned to the T2T-CHM13 assembly.</p></div><div><h3>Results</h3><p>We were able to resolve all 3 complex chromosome 21 rearrangements in which 15, 8, and 26 breakpoints were identified, respectively. By comparing the identified SV breakpoints, we were able to pinpoint a region between 21p13 and 21p12 that appears to be frequently involved in chromosome 21 rearrangements. Importantly, we observed acrocentric satellite DNA at several breakpoint junctions suggesting an important role for those elements in the formation of complex SVs.</p></div><div><h3>Conclusion</h3><p>Taken together, our results provide further insights into the architecture and underlying mechanisms of complex rearrangements on acrocentric chromosomes.</p></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424010094/pdfft?md5=1809b99be367e12f5c3447c0dac9c534&pid=1-s2.0-S2949774424010094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991137","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":"Author details for “Implementation of a digital patient-facing cancer family history tool in medically underserved populations”","authors":"","doi":"10.1016/j.gimo.2024.101860","DOIUrl":"10.1016/j.gimo.2024.101860","url":null,"abstract":"<div><h3>Purpose</h3><p>We developed an electronic patient-facing family history collection tool including B-RST 3.0, PREMM₅ risk assessments and “limited family knowledge/structure” information designed for primary care settings. We evaluated the tool’s performance compared with genetic-counselor-collected information for clinical risk stratification in a population with barriers to access.</p></div><div><h3>Methods</h3><p>English- or Spanish-speaking patients aged 18 to 49 were invited to participate. Individuals with limited family knowledge or at high or moderate risk based on their responses in the tool were offered genetic testing and counseling. We assessed overall agreement of family history collected in the tool compared with family history collected by the genetic counselors using Krippendorff’s alpha (K-alpha). Multivariable logistic regression was used to assess characteristics associated with inaccuracy.</p></div><div><h3>Results</h3><p>Most people (94%, <em>n</em> = 1711) who interacted with the tool completed it. Those included in the agreement analysis (<em>n</em> = 604) had a median age of 36.3 years, 81.6% were female, and 44.4% were Non-Hispanic White. Both the B-RST 3.0 and PREMM₅ had moderate agreement: 69.9% (K-alpha = .40, 95% CI [0.32, 0.47]) and 83.9% (K-alpha = .52, 95% CI [0.43, 0.60]), respectively. Agreement was high (96%) for people with clinically significant risk for one of the hereditary cancer syndromes. For B-RST 3.0, the factors significantly associated with inaccuracy were study site, sex, and race/ethnicity. For PREMM₅, age, sex, and education were associated with inaccuracy. Barriers to access were not associated with inaccuracy.</p></div><div><h3>Conclusion</h3><p>Implementation of this tool could increase identification of individuals at risk for hereditary cancer syndromes, including those with barriers to health care access.</p></div>","PeriodicalId":100576,"journal":{"name":"Genetics in Medicine Open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949774424010069/pdfft?md5=cef2c34c2a32865a2a655a8aed8eb140&pid=1-s2.0-S2949774424010069-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012210","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}