Genetics in Medicine最新文献

{"title":"Evolving knowledge of red flag clinical features associated with TTR p.(Val142Ile) in a diverse electronic health-record-linked biobank","authors":"Amy R. Kontorovich ,&nbsp;Connor B. Benson ,&nbsp;Alexandra McClellan ,&nbsp;Gillian M. Belbin ,&nbsp;Eimear E. Kenny ,&nbsp;Noura S. Abul-Husn","doi":"10.1016/j.gim.2024.101346","DOIUrl":"10.1016/j.gim.2024.101346","url":null,"abstract":"<div><h3>Purpose</h3><div>Previous studies have established red flags that raise clinical suspicion for the hereditary form of transthyretin amyloidosis (ATTRv). However, these have not been specifically evaluated for the most common associated variant, <em>TTR</em> p.(Val142Ile).</div></div><div><h3>Methods</h3><div>Using an ancestrally diverse electronic health-record-linked biobank with exome sequence data from 27,630 unrelated adults, we evaluated 9 ATTRv-related clinical features among <em>TTR</em> p.(Val142Ile)-positive and -negative individuals.</div></div><div><h3>Results</h3><div>Among 337 variant-positive individuals (median age 63, 60% female), 10 (3.0%) were diagnosed with amyloidosis. <em>TTR</em> p.(Val142Ile) was associated with increased odds of cardiomyopathy/heart failure (CM/HF), atrial fibrillation, polyneuropathy, carpal tunnel syndrome, and proteinuria, but only in individuals ≥60 years. These features were evident 1.7 to 7.7 years earlier in variant-positive vs -negative individuals (hazard ratio [HR] 1.37, <em>P</em> = 3.99 × 10⁻²; HR 1.78, <em>P</em> = 2.52 × 10⁻³; HR 1.78, <em>P</em> = 1.70 × 10⁻³; HR 1.81, <em>P</em> = 5.14 × 10⁻³; HR 1.60, <em>P</em> = 1.94 × 10⁻², respectively). By age 50, the cumulative incidence of CM/HF was 3.5-fold higher, and by age 60, the incidences of CM/HF, polyneuropathy, and proteinuria were 2-fold higher in variant-positive individuals.</div></div><div><h3>Conclusion</h3><div>This study clarifies red flags that are associated with <em>TTR</em> p.(Val142Ile) in an age-dependent manner. With modifying therapies being available, early diagnosis of ATTRv in variant-positive individuals through the recognition of key clinical features is paramount.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 3","pages":"Article 101346"},"PeriodicalIF":6.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating reproductive carrier screening using biotinidase deficiency as a model: Variants identified, variant rates, and management","authors":"Peter Benn ,&nbsp;Yang Wang ,&nbsp;Josie Gray ,&nbsp;Elizabeth Kramer Dugan ,&nbsp;Mark Hajjar ,&nbsp;Brittany Prigmore ,&nbsp;Vivienne Souter ,&nbsp;Barry Wolf","doi":"10.1016/j.gim.2024.101345","DOIUrl":"10.1016/j.gim.2024.101345","url":null,"abstract":"<div><h3>Purpose</h3><div>To review biotinidase gene (<em>BTD</em>) variants identified in a large, diverse, reproductive carrier screening (RCS) cohort and outline management of heterozygotes with pathogenic or likely pathogenic (P/LP) variants.</div></div><div><h3>Methods</h3><div>This retrospective observational study included samples tested from January 2020 to September 2022 in a 274-gene panel. The study involved females aged 18 to 55 years. Screening was performed using next-generation sequencing covering exons and 10 base-pair flanking introns. The heterozygote frequency was calculated for P/LP variants for the entire population and individual racial/ethnic groups.</div></div><div><h3>Results</h3><div>Of the 91,637 women tested, 5625 (6.1%) had a P/LP variant in <em>BTD</em>. NM_000060.4:c.1330G&gt;C p.(Asp444His) (referred to as D444H or D424H) alone, or in combination with another variant, accounted for 5193 (92.3%) of the positive tests. P/LP heterozygote rates differed between racial and ethnic groups. We ascertained 7 novel P/LP variants not previously recorded in databases.</div></div><div><h3>Conclusion</h3><div>The <em>BTD</em> P/LP variants identified through RCS were substantially compatible with those found through positive newborn screening. Therefore, RCS provides a potential for earlier diagnosis. We observed significant differences in P/LP heterozygote rates for biotinidase deficiency among different racial and ethnic groups. Most reported variants can be interpreted without requiring determination of serum biotinidase activity.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 3","pages":"Article 101345"},"PeriodicalIF":6.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing data sets","authors":"Ben Weisburd ,&nbsp;Rakshya Sharma ,&nbsp;Villem Pata ,&nbsp;Tiia Reimand ,&nbsp;Vijay S. Ganesh ,&nbsp;Christina Austin-Tse ,&nbsp;Ikeoluwa Osei-Owusu ,&nbsp;Emily O’Heir ,&nbsp;Melanie O’Leary ,&nbsp;Lynn Pais ,&nbsp;Seth A. Stafki ,&nbsp;Audrey L. Daugherty ,&nbsp;Chiara Folland ,&nbsp;Stojan Peric ,&nbsp;Nagia Fahmy ,&nbsp;Bjarne Udd ,&nbsp;Magda Horáková ,&nbsp;Anna Łusakowska ,&nbsp;Rajanna Manoj ,&nbsp;Atchayaram Nalini ,&nbsp;Anne O’Donnell-Luria","doi":"10.1016/j.gim.2024.101336","DOIUrl":"10.1016/j.gim.2024.101336","url":null,"abstract":"<div><h3>Purpose</h3><div>We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome, or panel sequencing data sets aligned to a GRCh37, GRCh38, or T2T reference genome.</div></div><div><h3>Methods</h3><div>The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the <em>SMN1</em> and <em>SMN2</em> paralogs. It uses these reads to determine whether an individual most likely has 0 functional copies of <em>SMN1</em>.</div></div><div><h3>Results</h3><div>We developed SMA Finder and evaluated it on 16,626 exomes and 3911 genomes from the Broad Institute Center for Mendelian Genomics, 1157 exomes and 8762 panel samples from Tartu University Hospital, and 198,868 exomes and 198,868 genomes from the UK Biobank.</div><div>SMA Finder’s false-positive rate was below 1 in 200,000 samples, its positive predictive value was greater than 96%, and its true-positive rate was 29 out of 29. Most of these SMA diagnoses had initially been clinically misdiagnosed as limb-girdle muscular dystrophy.</div></div><div><h3>Conclusion</h3><div>Our extensive evaluation of SMA Finder on exome, genome, and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, and the existence of treatment options, we propose that it is time to add <em>SMN1</em> to the American College of Medical Genetics list of genes with reportable secondary findings after genome and exome sequencing.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101336"},"PeriodicalIF":6.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation versus loss of function of NTRK2 in 44 affected individuals leads to 2 distinct neurodevelopmental disorders.","authors":"Eva Berger, Robin-Tobias Jauss, Judith D Ranells, Emir Zonic, Lydia von Wintzingerode, Ashley Wilson, Johannes Wagner, Annabelle Tuttle, Amanda Thomas-Wilson, Björn Schulte, Rachel Rabin, John Pappas, Jacqueline A Odgis, Osama Muthaffar, Alejandra Mendez-Fadol, Matthew Lynch, Jonathan Levy, Daphné Lehalle, Nicole J Lake, Ilona Krey, Mariya Kozenko, Ellen Knierim, Guillaume Jouret, Vaidehi Jobanputra, Bertrand Isidor, David Hunt, Tzung-Chien Hsieh, Alexander M Holtz, Tobias B Haack, Nina B Gold, Désirée Dunstheimer, Mylène Donge, Wallid Deb, Katlin A De La Rosa Poueriet, Magdalena Danyel, John Christodoulou, Saurabh Chopra, Bert Callewaert, Andreas Busche, Lauren Brick, Bary G Bigay, Marie Arlt, Swathi S Anikar, Mohammad N Almohammal, Deanna Almanza, Amal Alhashem, Aida Bertoli-Avella, Heinrich Sticht, Rami Abou Jamra","doi":"10.1016/j.gim.2024.101326","DOIUrl":"10.1016/j.gim.2024.101326","url":null,"abstract":"<p><strong>Purpose: </strong>Heterozygous pathogenic variants in NTRK2 (HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation.</p><p><strong>Methods: </strong>We reported an extended cohort of 44 affected individuals, of whom 19 are from the literature and 25 were previously unreported.</p><p><strong>Results: </strong>Our analysis led to splitting the cohort into 2 entities.</p><p><strong>Conclusion: </strong>One group had variants in the cholesterol-binding motif of the transmembrane domain, with most of these being the recurrent variant c.1301A>G p.(Tyr434Cys). These variants probably lead to upregulation of tropomyosin receptor kinase B activity and to a severe phenotype of developmental delay/intellectual disability, muscular hypotonia, therapy-refractory epilepsy, visual impairment and blindness, and feeding difficulties. The second group had truncating variants or variants that presumably disturb the 3D structure of the protein leading to loss of function. These individuals had a remarkably milder phenotype of developmental delay, obesity, and hyperphagia.</p>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":" ","pages":"101326"},"PeriodicalIF":6.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Horta et al","authors":"Abbe Lai ,&nbsp;Aubrie Soucy ,&nbsp;Edward Yang ,&nbsp;Timothy Yu ,&nbsp;Annapurna Poduri","doi":"10.1016/j.gim.2024.101215","DOIUrl":"10.1016/j.gim.2024.101215","url":null,"abstract":"","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"26 11","pages":"Article 101215"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries","authors":"Ronja Hotakainen ,&nbsp;Timo Järvinen ,&nbsp;Kaisa Kettunen ,&nbsp;Anna-Kaisa Anttonen ,&nbsp;Eveliina Jakkula","doi":"10.1016/j.gim.2024.101304","DOIUrl":"10.1016/j.gim.2024.101304","url":null,"abstract":"<div><h3>Purpose</h3><div>Monogenic rare diseases contribute significantly to infant deaths and pediatric hospitalizations and cause burden to the patients and their families. The American College of Medical Genetics and Genomics recommended in 2021 that carrier screening of autosomal recessive and X-linked conditions with a carrier frequency of ≥1/200 and a severe or moderate phenotype should be offered when planning or during pregnancy. In November 2023 gnomAD v4.0 was released. It contains in total 807,162 individuals, being nearly 5× larger than previous versions, which have been used to estimate gene carrier frequencies (GCF).</div></div><div><h3>Methods</h3><div>We utilized gnomAD v4.0 (GRCh38) to calculate the GCFs for available genetic ancestry groups for variants having pathogenic or likely pathogenic classification (&gt;80% of submissions) in ClinVar. We calculated GCF separately for exomes and genomes, combined data, and at-risk couple frequencies (ACF) per genetic ancestry group.</div></div><div><h3>Results</h3><div>In total, 324 genes had a GCF ≥1/200 in at least 1 ancestry subgroup. The number of genes with GCF ≥1/200 varied greatly between subgroups. ACFs were more similar, Ashkenazi Jewish having the highest ACF of 6.11%.</div></div><div><h3>Conclusion</h3><div>Improved understanding of carrier risks and updated carrier screening content would allow patients to make more informed reproductive decisions.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 1","pages":"Article 101304"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correspondence on “The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR, PIK3CA, and PIK3R2” by Lai et al","authors":"Edgar Horta ,&nbsp;Eric Dahlen ,&nbsp;Camille Engel ,&nbsp;Juliette Piard ,&nbsp;Christel Thauvin-Robinet ,&nbsp;Laurence Faivre ,&nbsp;Pierre Vabres ,&nbsp;Paul Kuentz","doi":"10.1016/j.gim.2024.101214","DOIUrl":"10.1016/j.gim.2024.101214","url":null,"abstract":"","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"26 11","pages":"Article 101214"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary care provider practices, attitudes, and confidence with hereditary cancer risk assessment and testing: A mixed methods study","authors":"Sarah Conner ,&nbsp;Tesla Theoryn ,&nbsp;Emerson Dusic ,&nbsp;Faith Beers ,&nbsp;Sarah Knerr ,&nbsp;Barbara Norquist ,&nbsp;Brian H. Shirts ,&nbsp;Deborah Bowen ,&nbsp;Elizabeth M. Swisher ,&nbsp;Catharine Wang","doi":"10.1016/j.gim.2024.101307","DOIUrl":"10.1016/j.gim.2024.101307","url":null,"abstract":"<div><h3>Purpose</h3><div>This study sought to better understand primary care providers’ readiness to conduct population-based risk assessment and offer genetic testing for hereditary cancer.</div></div><div><h3>Methods</h3><div>Sixty primary care providers completed a survey assessing their current practices, attitudes, and confidence with cancer risk assessment and testing. Sixteen participated in follow-up interviews. Descriptive statistics are presented and supported by qualitative data.</div></div><div><h3>Results</h3><div>Providers preferred direct questioning over standardized screening tools. In interviews, providers said they are not ordering cancer-risk genetic testing even when it might be appropriate. Ninety-eight percent agree testing is important to clinical care, but 73% agree that it could negatively affect patients. Ninety percent were willing to offer targeted testing, but only 68% were willing to offer population-based risk assessment. Confidence performing different behaviors necessary in a cancer risk assessment varied, with only 32% confident responding to questions specifically related to genetic testing.</div></div><div><h3>Conclusion</h3><div>Providers are willing to offer genetic testing but unlikely to do so because they lack confidence in genetics-specific skill areas. Unsystematic approaches to family history screening and fears about follow-up complexity may exacerbate health disparities. Interventions to increase provider confidence in ascertaining and managing hereditary cancer are needed to achieve widespread adoption of population-based risk assessment and guideline-recommended genetic testing.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 4","pages":"Article 101307"},"PeriodicalIF":6.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in and predictors of patient pharmacogenomic test uptake in a national health care system","authors":"Abigail Silva ,&nbsp;Deepak Voora ,&nbsp;Rebekah Ryanne Wu ,&nbsp;Brian Bartle ,&nbsp;Catherine Chanfreau-Coffinier ,&nbsp;Allison Hung ,&nbsp;Corrine I. Voils","doi":"10.1016/j.gim.2024.101308","DOIUrl":"10.1016/j.gim.2024.101308","url":null,"abstract":"<div><h3>Purpose</h3><div>Better understanding patient uptake of pharmacogenomic (PGx) testing may inform its implementation and maximize the benefits that such testing can confer. This study examined patient and provider factors associated with PGx test ordering in a national health care system in which panel-based testing was implemented as part of routine care.</div></div><div><h3>Methods</h3><div>We used a retrospective matched cohort design and data from the Veterans Health Administration Corporate Data Warehouse. A conditional logistic model was used to identify factors associated with a PGx order receipt and estimate odds ratios and 95% confidence intervals.</div></div><div><h3>Results</h3><div>The following patient factors predicted receipt of a PGx test order: younger age, married status, rural residence, non-Hispanic Black or Hispanic race/ethnicity, PGx educational mailer receipt, depression diagnosis, allergy to a drug on the panel, prescriptions for drugs on the panel, and specialty care visits (<em>P &lt; .</em>05). Additionally, patients whose providers were female, younger, a nurse practitioner/physician assistant or pharmacist, or participated in an educational mailer program were more likely to receive an order (<em>P &lt; .</em>05).</div></div><div><h3>Conclusion</h3><div>This study highlights factors that may facilitate or hinder the widespread and equitable implementation of PGx testing in a large national health care system. The information is being used to further refine the program.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 3","pages":"Article 101308"},"PeriodicalIF":6.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinician-reported Genetic Testing Utility Index (C-GUIDE) for Prenatal Care: Initial evidence of content and construct validity","authors":"Robin Z. Hayeems ,&nbsp;Stephanie Luca ,&nbsp;Bowen Xiao ,&nbsp;Christie Boswell-Patterson ,&nbsp;Carolina Lavin Venegas ,&nbsp;Clarissa R. Abi Semaan ,&nbsp;Tessa Kolar ,&nbsp;Diane Myles-Reid ,&nbsp;Lauren Chad ,&nbsp;David Dyment ,&nbsp;Kym M. Boycott ,&nbsp;Joanna Lazier ,&nbsp;Wendy J. Ungar ,&nbsp;Christine M. Armour","doi":"10.1016/j.gim.2024.101306","DOIUrl":"10.1016/j.gim.2024.101306","url":null,"abstract":"<div><h3>Purpose</h3><div>To develop and assess the face and construct validity of the Clinician-reported Genetic Testing Utility Index (C-GUIDE) for genetic testing in prenatal care.</div></div><div><h3>Methods</h3><div>After a literature review and consultation with clinical experts, a preliminary draft of C-GUIDE Prenatal was developed. Its face and content validity were then assessed by 19 prenatal genetics’ providers using interviews and surveys. Feedback informed further revisions. To test construct validity, 4 geneticist raters completed C-GUIDE on a retrospective sample of cases that received prenatal genetic testing and completed a concurrent global assessment of utility of these cases using an anchor item. A generalized estimating equations model was used to adjust for rater correlation and measure the association between C-GUIDE scores, global item scores, and potential clinical variables.</div></div><div><h3>Results</h3><div>To develop C-GUIDE Prenatal, 7 items were removed, 10 items were modified, and 4 items were added. For 101 cases rated for validation, on average, a 1-point increase in the global item score was associated with an increase of 1.1 in the C-GUIDE score (<em>P</em> = .04). Compared with uninformative results, informative positive and informative negative results were associated with a mean increase of 10.7 (SE = 1.05) (<em>P</em> &lt; .001) and 5.6 (SE = 1.85) (<em>P</em> &lt; .001), respectively. As indications for testing, known/familial variants were associated with a mean increase in the C-GUIDE score of 4.7 (SE = 2.21) (<em>P</em> &lt; .001) compared with ultrasound findings. C-GUIDE scores increased by a mean of 3.0 (SE = 0.23) among cases for whom pregnancies were ongoing compared with those for whom they were not (<em>P</em> &lt; .01).</div></div><div><h3>Conclusion</h3><div>The significant positive associations between C-GUIDE total and the global item score and between C-GUIDE total, result type, indication for testing, and pregnancy status in the expected directions provide evidence of construct validity.</div></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"27 1","pages":"Article 101306"},"PeriodicalIF":6.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}