73 results on '"Sara Fitzgerald"'
Search Results
2. A multicenter cross-sectional study in infants with congenital heart defects demonstrates high diagnostic yield of genetic testing but variable evaluation practices
- Author
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Matthew D. Durbin, Lindsey R. Helvaty, Ming Li, William Border, Sara Fitzgerald-Butt, Vidu Garg, Gabrielle C. Geddes, Benjamin M. Helm, Seema R. Lalani, Kim L. McBride, Alexis McEntire, Dana K. Mitchell, Chaya N. Murali, Stephanie B. Wechsler, Benjamin J. Landis, and Stephanie M. Ware
- Subjects
Cardiovascular genetics ,Congenital heart disease ,Genetic testing ,Genetics ,QH426-470 ,Medicine - Abstract
Purpose: For patients with congenital heart disease (CHD), the most common birth defect, genetic evaluation is not universally accepted, and current practices are anecdotal. Here, we analyzed genetic evaluation practices across centers, determined diagnostic yield of testing, and identified phenotypic features associated with abnormal results. Methods: This is a multicenter cross-sectional study of 5 large children’s hospitals, including 2899 children ≤14 months undergoing surgical repair for CHD from 2013 to 2016, followed by multivariate logistics regression analysis. Results: Genetic testing occurred in 1607 of 2899 patients (55%). Testing rates differed highly between institutions (42%-78%, P < .001). Choice of testing modality also differed across institutions (ie, chromosomal microarray, 26%-67%, P < .001). Genetic testing was abnormal in 702 of 1607 patients (44%), and no major phenotypic feature drove diagnostic yield. Only 849 patients were seen by geneticists (29%), ranging across centers (15%-52%, P < .001). Geneticist consultation associated with increased genetic testing yield (odds ratio: 5.7, 95% CI 4.33-7.58, P < .001). Conclusion: Genetics evaluation in CHD is diagnostically important but underused and highly variable, with high diagnostic rates across patient types, including in infants with presumed isolated CHD. These findings support recommendations for comprehensive testing and standardization of care.
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- 2023
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- View/download PDF
3. Novel frameshift variant in MYL2 reveals molecular differences between dominant and recessive forms of hypertrophic cardiomyopathy.
- Author
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Sathiya N Manivannan, Sihem Darouich, Aida Masmoudi, David Gordon, Gloria Zender, Zhe Han, Sara Fitzgerald-Butt, Peter White, Kim L McBride, Maher Kharrat, and Vidu Garg
- Subjects
Genetics ,QH426-470 - Abstract
Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the ventricular muscle without dilation and is often associated with dominant pathogenic variants in cardiac sarcomeric protein genes. Here, we report a family with two infants diagnosed with infantile-onset HCM and mitral valve dysplasia that led to death before one year of age. Using exome sequencing, we discovered that one of the affected children had a homozygous frameshift variant in Myosin light chain 2 (MYL2:NM_000432.3:c.431_432delCT: p.Pro144Argfs*57;MYL2-fs), which alters the last 20 amino acids of the protein and is predicted to impact the most C-terminal of the three EF-hand domains in MYL2. The parents are unaffected heterozygous carriers of the variant and the variant is absent in control cohorts from gnomAD. The absence of the phenotype in carriers and the infantile presentation of severe HCM is in contrast to HCM associated with dominant MYL2 variants. Immunohistochemical analysis of the ventricular muscle of the deceased patient with the MYL2-fs variant showed a marked reduction of MYL2 expression compared to an unaffected control. In vitro overexpression studies further indicate that the MYL2-fs variant is actively degraded. In contrast, an HCM-associated missense variant (MYL2:p.Gly162Arg) and three other MYL2 stop-gain variants (p.E22*, p.K62*, p.E97*) that result in loss of the EF domains are stably expressed but show impaired localization. The degradation of the MYL2-fs can be rescued by inhibiting the cell's proteasome function supporting a post-translational effect of the variant. In vivo rescue experiments with a Drosophila MYL2-homolog (Mlc2) knockdown model indicate that neither the MYL2-fs nor the MYL2:p.Gly162Arg variant supports normal cardiac function. The tools that we have generated provide a rapid screening platform for functional assessment of variants of unknown significance in MYL2. Our study supports an autosomal recessive model of inheritance for MYL2 loss-of-function variants in infantile HCM and highlights the variant-specific molecular differences found in MYL2-associated cardiomyopathy.
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- 2020
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- View/download PDF
4. Illustrations
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Sara Fitzgerald
- Published
- 2011
5. Frontmatter
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Sara Fitzgerald
- Published
- 2011
6. Notes
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Sara Fitzgerald
- Published
- 2011
7. Cover
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Sara Fitzgerald
- Published
- 2011
8. 7. Back to Washington
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Sara Fitzgerald
- Published
- 2011
9. 12. The Turning Point
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Sara Fitzgerald
- Published
- 2011
10. Epilogue
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Sara Fitzgerald
- Published
- 2011
11. 11. A New Crusade
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Sara Fitzgerald
- Published
- 2011
12. 10. The Show
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Sara Fitzgerald
- Published
- 2011
13. 9. A Path out of Exile
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Sara Fitzgerald
- Published
- 2011
14. 8. A Crisis of Conscience
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Sara Fitzgerald
- Published
- 2011
15. 5. The Click Moment
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Sara Fitzgerald
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- 2011
16. 6. Minding the Middle [Includes Image Plates]
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Sara Fitzgerald
- Published
- 2011
17. 2. Hooked on Politics
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Sara Fitzgerald
- Published
- 2011
18. 3. A Chapeau in the Ring
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Sara Fitzgerald
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- 2011
19. 1. The Girl from New Berlin
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Sara Fitzgerald
- Published
- 2011
20. 4. The Reluctant Candidate
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Sara Fitzgerald
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- 2011
21. Prologue
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Sara Fitzgerald
- Published
- 2011
22. Clinical exome sequencing reports: current informatics practice and future opportunities.
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Rajeswari Swaminathan, Yungui Huang, Caroline Astbury, Sara Fitzgerald-Butt, Katherine Miller, Justin Cole, Christopher W. Bartlett, and Simon M. Lin
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- 2017
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23. The Love of Her Life
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Sara Fitzgerald
- Published
- 2022
- Full Text
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24. Effect of manganese substitution of ferrite nanoparticles on particle grain structure
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Zichun Yan, Anish Chaluvadi, Sara FitzGerald, Sarah Spence, Christopher Bleyer, Jiazhou Zhu, Thomas M. Crawford, Rachel B. Getman, John Watt, Dale L. Huber, and O. Thompson Mefford
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General Engineering ,General Materials Science ,Bioengineering ,General Chemistry ,Atomic and Molecular Physics, and Optics - Abstract
Manganese substitution induces crystallite shrinkage and loss of saturation magnetization for the manganese ferrite nanoparticles synthesized by thermal decomposition.
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- 2022
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25. Management of amended variant classification laboratory reports by genetic counselors in the United States and Canada: An exploratory study
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Brooke Richardson, Amy M. Breman, Leah Wetherill, Benjamin M. Helm, Sara Fitzgerald-Butt, and Katherine G. Spoonamore
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Duty to Recontact ,Protocol (science) ,medicine.medical_specialty ,medicine.diagnostic_test ,Genetic counseling ,Exploratory research ,Genetic Counseling ,Ordering Physician ,United States ,Preference ,Counselors ,Surveys and Questionnaires ,Family medicine ,medicine ,Humans ,Medical genetics ,Genetic Testing ,Psychology ,Genetics (clinical) ,Standard operating procedure ,Genetic testing - Abstract
For the past two decades, the guidelines put forth by the American College of Medical Genetics and Genomics (ACMG) detailing providers' clinical responsibility to recontact patients have remained mostly unchanged, despite evolving variant interpretation practices which have yielded substantial rates of reclassification and amended reports. In fact, there is little information regarding genetic counselors' roles in informing patients of reclassified variants, or the process by which these amended reports are currently being handled. In this study, we developed a survey to measure current experiences with amended variant reports and preferences for ideal management, which was completed by 96 genetic counselors from the United States and Canada. All respondents indicated they were the individuals responsible for disclosing initial positive genetic testing results and any clinically actionable reclassified variant reports, and over half (56%) received at least a few amended variant reports each year. Nearly a quarter (20/87) of respondents reported having a standard operating procedure (SOP) for managing amended reports and all were very satisfied (12/20) or satisfied (8/20) with the SOP. Of those without a protocol, 76% (51/67) would prefer to have an SOP implemented. Respondents reported a preference for (1) laboratories to send amended variant reports directly to the genetic counselor or ordering physician through email or an online portal, and (2) notification to patients ideally occurring through a phone call. In the event that the original genetic counselor is inaccessible, respondents reported a preference for reports to be sent directly to another genetic counselor (36%) on the team or the clinic in general (27%). Information from this study provides insight into the current practices of genetic counselors as applied to amended reports and what improvements may increase the efficiency of the reporting process. Moreover, these results suggest a need for an updated statement addressing duty to recontact, specifically as it applies to amended variant reports.
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- 2021
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26. Genetic counseling for congenital heart disease – Practice resource of the National Society of Genetic Counselors
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Emily Leann Griffin, Sara Fitzgerald-Butt, Katie L. Ziegler, Matthew J Thomas, Allison F. Schartman, Benjamin M. Helm, Erin Syverson, Hannah E. Ison, Kristyne M. Stone, Erin M. Demo, Amy R. Shikany, Ashley Parrott, Lindsay Meyers, and Kristi K Fitzgerald
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Counseling ,Heart Defects, Congenital ,medicine.medical_specialty ,Certification ,medicine.diagnostic_test ,Heart disease ,Genetic counseling ,Complex disease ,medicine.disease ,Counselors ,Resource (project management) ,Family medicine ,Genetic screening ,medicine ,Humans ,Psychology ,Genetics (clinical) ,Congenital heart disease ,Genetic testing - Abstract
Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre- and postnatally.
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- 2021
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27. Searching for Emily Hale
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Sara Fitzgerald
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- 2021
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28. In Her Own Words
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Frances Dickey and Sara Fitzgerald
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- 2021
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29. Emily Hale
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Sara Fitzgerald
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- 2021
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30. Interplay between Thermal and Magnetic properties of Polymer Nanocomposites with Superparamagnetic Fe3O4 Nanoparticles
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Md Rezoanur Rahman, Abdulhakim Bake, Jumlat Al Ahmed, Sheik Md Kazi Nazrul Islam, Liang Wu, Hadis Khakbaz, Sara FitzGerald, Artek Chalifour, Karen L. Livesey, Jonathan C. Knott, Peter C. Innis, Stephen Beirne, and David Cortie
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Condensed Matter Physics ,Electronic, Optical and Magnetic Materials - Published
- 2023
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31. Pediatric Mixed Left Ventricular Non-Compaction and Restrictive Cardiomyopathy Bridged to Heart Transplant with Ventricular Assist
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Robert J. Gajarski, Sara Fitzgerald-Butt, Ashley B. Hodge, Adam Morrison, Patrick I. McConnell, Peter B. Baker, and Deipanjan Nandi
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Restrictive cardiomyopathy ,Cardiomyopathy ,medicine.disease ,Left ventricular noncompaction cardiomyopathy ,Asymptomatic ,Transplantation ,Ventricular assist device ,Heart failure ,Internal medicine ,medicine ,Cardiology ,MYH7 ,medicine.symptom ,business - Abstract
Left ventricular noncompaction cardiomyopathy (LVNC) is a rare form of heritable cardiomyopathy with wide genotypic variability, numerous phenotypic variations, and a wide spectrum of clinical disease from asymptomatic to end stage heart failure. Here, we present a case of a 2-year-old boy who presented to their pediatrician with a cough as a first clinical sign of heart failure, rapidly progressing to severe heart failure. He was found to have mixed LVNC with a restrictive phenotype, a rare phenotype of this form of cardiomyopathy. Eventually, the patient was supported via mechanical circulation with a Berlin Heart EXCOR® ventricular assist device as bridge to successful cardiac transplantation. Genetic testing for inherited cardiomyopathies found a mutation in MYH7 (Arg369Gln), known to be associated with various forms of cardiomyopathy, but has not been reported in restrictive LVNC.
- Published
- 2020
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32. The Silenced Muse : Emily Hale, T. S. Eliot, and the Role of a Lifetime
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Sara Fitzgerald and Sara Fitzgerald
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- Drama teachers--United States--Biography, Authors, American--20th century--Biography
- Abstract
The first full-length biography of the longtime secret love of the celebrated poet T. S. Eliot, Emily Hale, called'heartbreaking'by Publishers Weekly and The Washington Post calls'a meticulously researched book that reads like a novel.”In January 2020, the largest and most eagerly awaited cache of new materials written by the Nobel-Prize-winning poet T. S. Eliot was finally opened: the 1,131 letters he sent Emily Hale, his little-known American love. But even as Eliot scholars explore Hale's impact on Eliot's work, a tantalizing question has not been fully answered: who was Emily Hale?Sara Fitzgerald's The Silenced Muse: Emily Hale, T. S. Eliot, and the Role of a Lifetime is the first full-length biography devoted to Hale, telling her side of a complicated relationship. Based on the embargoed letters and Fitzgerald's extensive research into Hale's life and times, this book brings to light that Hale was much more than just a muse to a literary celebrity. Hale overcame personal hardship to pursue a career as a professor of speech and drama at prominent American women's colleges and schools. She was a talented amateur actress and director, sharing the stage with others who went on to notable professional careers. Behind the scenes, she also guided Eliot as he began to explore playwriting with works such as Murder in the Cathedral. Hale's story is challenging to wholly uncover because the Boston clergyman's daughter was by nature reticent and humble. More critically, Eliot arranged for nearly all of her letters to be destroyed. The Silenced Muse finally reveals that Hale's story is not that of a lover scorned, but rather a woman who was herself gifted and celebrated by her students and peers.
- Published
- 2024
33. Conquering Heroines
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Sara Fitzgerald
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- 2020
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34. eP118: Connective tissue disorders not otherwise specified: Defining the problem
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Lindsey Elmore, Sara Fitzgerald-Butt, Gabrielle Geddes, Benjamin Helm, Melissa Lah, Benjamin Landis, Larry Markham, Lauren Rosier, Kelly Schmit, Katherine Spoonamore, Courtney Vujakovich, Theodore Wilson, and Stephanie Ware
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Genetics (clinical) - Published
- 2022
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35. Clinical exome sequencing reports: current informatics practice and future opportunities
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Simon Lin, Katherine E. Miller, Christopher W. Bartlett, Caroline Astbury, Rajeswari Swaminathan, Sara Fitzgerald-Butt, Yungui Huang, and Justin W. Cole
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Research Report ,0301 basic medicine ,Vocabulary ,media_common.quotation_subject ,Reviews ,Guidelines as Topic ,Health Informatics ,03 medical and health sciences ,Controlled vocabulary ,Humans ,Medicine ,Exome ,Genetic Testing ,Exome sequencing ,media_common ,Genetic testing ,Common Data Elements ,medicine.diagnostic_test ,business.industry ,Sequence Analysis, DNA ,Data science ,030104 developmental biology ,Data extraction ,Informatics ,Personalized medicine ,Laboratories ,business - Abstract
The increased adoption of clinical whole exome sequencing (WES) has improved the diagnostic yield for patients with complex genetic conditions. However, the informatics practice for handling information contained in whole exome reports is still in its infancy, as evidenced by the lack of a common vocabulary within clinical sequencing reports generated across genetic laboratories. Genetic testing results are mostly transmitted using portable document format, which can make secondary analysis and data extraction challenging. This paper reviews a sample of clinical exome reports generated by Clinical Laboratory Improvement Amendments–certified genetic testing laboratories at tertiary-care facilities to assess and identify common data elements. Like structured radiology reports, which enable faster information retrieval and reuse, structuring genetic information within clinical WES reports would help facilitate integration of genetic information into electronic health records and enable retrospective research on the clinical utility of WES. We identify elements listed as mandatory according to practice guidelines but are currently missing from some of the clinical reports, which might help to organize the data when stored within structured databases. We also highlight elements, such as patient consent, that, although they do not appear within any of the current reports, may help in interpreting some of the information within the reports. Integrating genetic and clinical information would assist the adoption of personalized medicine for improved patient care and outcomes.
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- 2017
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36. At the Heart of the Pregnancy: What Prenatal and Cardiovascular Genetic Counselors Need to Know about Maternal Heart Disease
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Ana Morales, Amy R. Shikany, Crystal Tichnell, Sara Spencer, W. Aaron Kay, Katherine G. Spoonamore, Harikrishna Tandri, Patricia Arscott, Sara Fitzgerald-Butt, Christi Munn, Emily James, Brittney Murray, Emily Smith, Gretchen MacCarrick, Dawn C. Allain, and Jessica D. Kushner
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Adult ,medicine.medical_specialty ,Evidence-based practice ,Heart disease ,Genetic counseling ,Pregnancy Complications, Cardiovascular ,Population ,Genetic Counseling ,030204 cardiovascular system & hematology ,Subspecialty ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Prenatal Diagnosis ,Humans ,Medicine ,030212 general & internal medicine ,Intensive care medicine ,education ,Genetics (clinical) ,education.field_of_study ,business.industry ,Public health ,medicine.disease ,Counselors ,Cardiovascular Diseases ,Physical therapy ,Female ,business ,Psychosocial - Abstract
In the last decade, an increasing number of cardiac conditions have been shown to have a genetic basis. Cardiovascular genetic counseling has emerged as a subspecialty aiming to identify unaffected at-risk individuals. An important sector of this at-risk population also includes expectant mothers, in whom unique clinical challenges may arise. Genetic counselors, especially those in cardiovascular and prenatal settings, have an opportunity to identify and assist women who may benefit from cardiovascular care during pregnancy. This paper provides basic management and genetic evaluation principles for affected women, as well as guidance on identifying those who are at risk. We provide considerations for cardiac surveillance in pregnancy and the post-partum period. Finally, key psychosocial issues that appraise how to best provide support to at risk women as they make informed decisions are discussed. We propose that a team approach including cardiology, maternal fetal medicine, and genetic counseling best serves this patient population. Ongoing questions addressing an evidence based approach to cardiovascular genetic conditions in pregnancy still remain. Thus, well-designed research protocols are essential to mark progress in this area.
- Published
- 2017
- Full Text
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37. Novel frameshift variant in MYL2 reveals molecular differences between dominant and recessive forms of hypertrophic cardiomyopathy
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Sara Fitzgerald-Butt, Sathiya N. Manivannan, Gloria Zender, Sihem Darouich, Aida Masmoudi, Maher Kharrat, Vidu Garg, Peter White, Zhe Han, David M Gordon, and Kim L. McBride
- Subjects
Proband ,Male ,Cancer Research ,Cardiomyopathy ,QH426-470 ,Biochemistry ,Infant Death ,Animals, Genetically Modified ,Consanguinity ,0302 clinical medicine ,Contractile Proteins ,Fatal Outcome ,Medicine and Health Sciences ,Missense mutation ,Frameshift Mutation ,Genetics (clinical) ,Exome sequencing ,Cells, Cultured ,Genes, Dominant ,Genetics ,0303 health sciences ,Drosophila Melanogaster ,Hypertrophic cardiomyopathy ,Eukaryota ,Heart ,Animal Models ,Pedigree ,Insects ,Phenotype ,Experimental Organism Systems ,Hyperexpression Techniques ,Drosophila ,Female ,Anatomy ,Cardiomyopathies ,Research Article ,Adult ,Heterozygote ,Myosin Light Chains ,Arthropoda ,Cardiac Ventricles ,Motor Proteins ,Actin Motors ,Cardiology ,Mouse Models ,Genes, Recessive ,Biology ,Myosins ,Research and Analysis Methods ,Frameshift mutation ,03 medical and health sciences ,Model Organisms ,Molecular Motors ,medicine ,Gene Expression and Vector Techniques ,Animals ,Humans ,Family ,Allele ,Molecular Biology Techniques ,Gene ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Alleles ,030304 developmental biology ,Molecular Biology Assays and Analysis Techniques ,Myocardium ,Siblings ,Organisms ,Infant, Newborn ,Biology and Life Sciences ,Proteins ,Infant ,Heterozygote advantage ,Cell Biology ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Invertebrates ,Cytoskeletal Proteins ,MYL2 ,Genetic Loci ,Animal Studies ,Cardiovascular Anatomy ,Cardiac Myosins ,030217 neurology & neurosurgery - Abstract
Hypertrophic cardiomyopathy (HCM) is characterized by thickening of the ventricular muscle without dilation and is often associated with dominant pathogenic variants in cardiac sarcomeric protein genes. Here, we report a family with two infants diagnosed with infantile-onset HCM and mitral valve dysplasia that led to death before one year of age. Using exome sequencing, we discovered that one of the affected children had a homozygous frameshift variant in Myosin light chain 2 (MYL2:NM_000432.3:c.431_432delCT: p.Pro144Argfs*57;MYL2-fs), which alters the last 20 amino acids of the protein and is predicted to impact the most C-terminal of the three EF-hand domains in MYL2. The parents are unaffected heterozygous carriers of the variant and the variant is absent in control cohorts from gnomAD. The absence of the phenotype in carriers and the infantile presentation of severe HCM is in contrast to HCM associated with dominant MYL2 variants. Immunohistochemical analysis of the ventricular muscle of the deceased patient with the MYL2-fs variant showed a marked reduction of MYL2 expression compared to an unaffected control. In vitro overexpression studies further indicate that the MYL2-fs variant is actively degraded. In contrast, an HCM-associated missense variant (MYL2:p.Gly162Arg) and three other MYL2 stop-gain variants (p.E22*, p.K62*, p.E97*) that result in loss of the EF domains are stably expressed but show impaired localization. The degradation of the MYL2-fs can be rescued by inhibiting the cell’s proteasome function supporting a post-translational effect of the variant. In vivo rescue experiments with a Drosophila MYL2-homolog (Mlc2) knockdown model indicate that neither the MYL2-fs nor the MYL2:p.Gly162Arg variant supports normal cardiac function. The tools that we have generated provide a rapid screening platform for functional assessment of variants of unknown significance in MYL2. Our study supports an autosomal recessive model of inheritance for MYL2 loss-of-function variants in infantile HCM and highlights the variant-specific molecular differences found in MYL2-associated cardiomyopathy., Author summary We report a novel frameshift variant in MYL2 that is associated with a severe form of infantile-onset hypertrophic cardiomyopathy. The impact of the variant is only observed in the recessive form of the disease found in the proband and not in the parents who are carriers of the variant. This contrasts with other dominant variants in MYL2 that are associated with cardiomyopathies. We compared the stability of this variant to that of other cardiomyopathy associated MYL2 variants and found molecular differences that correlated with disease pathology. We also show different protein domain requirements for stability and localization of MYL2 in cardiomyocytes. Furthermore, we used a fly model to demonstrate functional deficits due to the variant in the developing heart. Overall, our study shows a molecular mechanism by which loss-of-function variants in MYL2 are recessive while missense variants are dominant. We highlight the use of exome sequencing and functional testing to assist in the diagnosis of rare forms of disease where pathogenicity of the variant is not obvious. The new tools we developed for in vitro functional study and the fly fluorescent reporter analysis will permit rapid analysis of MYL2 variants of unknown significance.
- Published
- 2019
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38. Reclassification of Variants of Uncertain Significance in Children with Inherited Arrhythmia Syndromes is Predicted by Clinical Factors
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Shalini C. Reshmi, Vidu Garg, Jeffrey S Bennett, Kim L. McBride, Anna Kamp, Madison Bernhardt, Naomi J. Kertesz, Erik Zmuda, and Sara Fitzgerald-Butt
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Male ,medicine.medical_specialty ,Adolescent ,Genomics ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Clinical information ,Medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Child ,Uncertain significance ,Genetic testing ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Electronic medical record ,Infant ,Arrhythmias, Cardiac ,Syndrome ,Clinical Practice ,030228 respiratory system ,Relative risk ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Practice Guidelines as Topic ,Medical genetics ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Genetic testing is important to augment clinical diagnosis and inform management of inherited arrhythmias syndromes (IAS), but variants of uncertain significance (VUS) are common and remain a challenge in clinical practice. In 2015, American College of Medical Genetics (ACMG) published updated guidelines for interpretation of genetic results. Despite increasing understanding of human genomic variation, there are no guidelines for reinterpretation of prior genetic test results. Patients at a single tertiary children's hospital with genetic testing for an IAS that demonstrated a VUS were re-evaluated using 2015 ACMG guidelines, clinical information, and publically available databases. Search of the electronic medical record identified 116 patients with genetic testing results available, and 24/116 (21%) harbored a VUS for an IAS. 23 unique VUS were evaluated from 12 genes. Over half of the VUS (12/23 (52%)) were reclassified using 2015 criteria, and 8 (35%) changed to pathogenic and 4 (17%) to benign. Relative risk of reclassification of VUS to a pathogenic variant in a patient with confirmed clinical diagnosis was 4.1 (95% CI 1.23-15.4). Reclassification was not associated with initial testing year. These data demonstrate 52% of VUS in children with IAS are reclassified with application of 2015 ACMG guidelines. Strength of phenotyping is associated with eventual pathogenic classification of genetic variants and periodic re-evaluation of VUS identified on genetic testing for IAS is warranted.
- Published
- 2019
39. The Responsibility to Recontact Research Participants after Reinterpretation of Genetic and Genomic Research Results
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Jennifer K. Wagner, Leila Jamal, Jason L. Vassy, Howard P. Levy, Tanya N. Nelson, Cynthia A. James, Julie Richer, Yvonne Bombard, Jennifer B. McCormick, Gail P. Jarvik, Sara Fitzgerald-Butt, Heidi L. Rehm, Kelly E. Ormond, Nanibaa’ A. Garrison, and Emmanuelle Souzeau
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Canada ,Research Subjects ,Genetic counseling ,Genetics, Medical ,Context (language use) ,030105 genetics & heredity ,Ethics, Research ,03 medical and health sciences ,Genetics ,medicine ,Humans ,Obligation ,Genetic Testing ,Workgroup ,Genetics (clinical) ,Societies, Medical ,Reinterpretation ,Duty to Recontact ,Medical education ,Australia ,Liability, Legal ,Genomics ,16. Peace & justice ,Human genetics ,United States ,Europe ,ASHG Position Statement ,030104 developmental biology ,Alliance ,Medical genetics ,Psychology ,Duty to Warn - Abstract
The evidence base supporting genetic and genomic sequence-variant interpretations is continuously evolving. An inherent consequence is that a variant's clinical significance might be reinterpreted over time as new evidence emerges regarding its pathogenicity or lack thereof. This raises ethical, legal, and financial issues as to whether there is a responsibility to recontact research participants to provide updates on reinterpretations of variants after the initial analysis. There has been discussion concerning the extent of this obligation in the context of both research and clinical care. Although clinical recommendations have begun to emerge, guidance is lacking on the responsibilities of researchers to inform participants of reinterpreted results. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in November 2018. The workgroup included representatives from the National Society of Genetic Counselors, the Canadian College of Medical Genetics, and the Canadian Association of Genetic Counsellors. The final statement includes twelve position statements that were endorsed or supported by the following organizations: Genetic Alliance, European Society of Human Genetics, Canadian Association of Genetic Counsellors, American Association of Anthropological Genetics, Executive Committee of the American Association of Physical Anthropologists, Canadian College of Medical Genetics, Human Genetics Society of Australasia, and National Society of Genetic Counselors.
- Published
- 2019
40. Manganese and cobalt substituted ferrite nanoparticles synthesized via a seed-mediated drip method
- Author
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O. Thompson Mefford, Zichun Yan, Sara FitzGerald, and Thomas M. Crawford
- Subjects
Materials science ,chemistry ,Ferrite nanoparticles ,chemistry.chemical_element ,General Materials Science ,Seed mediated ,Manganese ,Condensed Matter Physics ,Cobalt ,Atomic and Molecular Physics, and Optics ,Nuclear chemistry - Abstract
To produce multi-dopant ferrite nanoparticles, the ‘Extended LaMer’ and seed-mediated growth techniques were combined by first utilizing traditional thermal decomposition of metal acetylacetonates to produce seed particles, followed by a continuous injection of metal oleate precursors to increase the volume of the seed particles. With the choice of precursors for the seeding and dripping stage, we successfully synthesized particles with manganese precursor for seeding and cobalt precursor for dripping (Mn0.18Co1.04Fe1.78O4, 17.6 ± 3.3 nm), and particles with cobalt precursors for seeding and manganese precursors for dripping (Mn0.31Co0.74Fe1.95O4, 19.0 ± 1.9 nm). Combining transmission electron microscopy, energy-dispersive x-ray spectroscopy, x-ray diffraction, and vibrating sample magnetometry, we conclude that the seed-mediated drip method is a viable method to produce multi-dopant ferrite nanoparticles, and the size of the particles was mostly determined by the seeding stage, while the magnetic properties were more affected by the dripping stage.
- Published
- 2021
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41. Conquering Heroines : How Women Fought Sex Bias at Michigan and Paved the Way for Title IX
- Author
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Sara Fitzgerald and Sara Fitzgerald
- Subjects
- Sex discrimination against women--Michigan--Ann Arbor--History--20th century, Women civil rights workers--Michigan--Ann Arbor--History--20th century, Sex discrimination in higher education--Michigan--Ann Arbor--History--20th century, Sex discrimination in employment--Michigan--Ann Arbor--History--20th century
- Abstract
In 1970, a group of women in Ann Arbor launched a crusade with an objective that seemed beyond reach at the time—force the University of Michigan to treat women the same as men. Sex discrimination was then rampant at U-M. The school's admissions officials sought to maintain a ratio of 55:45 between male and female undergraduate entrants, turning away more qualified female applicants and arguing, among other things, that men needed help because they were less mature and posted lower grades. Women comprised less than seven percent of the University's faculty members and their salaries trailed their male peers by substantial amounts. As one administrator put it when pressed about the disparity, “Men have better use for the extra money.” Galvanized by their shared experiences with sex discrimination, the Ann Arbor women organized a group called FOCUS on Equal Employment for Women, led by activist Jean Ledwith King. Working with Bernice Sandler of the Women's Equity Action League, they developed a strategy to unleash the power of another powerful institution—the federal government—to demand change at U-M and, they hoped, across the world of higher education. Prompted by a complaint filed by FOCUS, the U.S. Department of Health, Education, and Welfare soon documented egregious examples of discrimination in Michigan's practices toward women and threatened to withhold millions of dollars in contracts unless the school adopted remedies. Among the hundreds of similar complaints filed against U.S. colleges in 1970–1971, the one brought by the Michigan women achieved the breakthrough that provided the historic template for settlements with other institutions. Drawing on oral histories from archives as well as new interviews with living participants, Conquering Heroines chronicles this pivotal period in the histories of the University of Michigan and the women's movement. An incredible story of grassroots activism and courageous women, the book highlights the kind of relentless effort that has helped make inclusivity an ongoing goal at U-M.
- Published
- 2020
42. Utilization of Whole Exome Sequencing to Identify Causative Mutations in Familial Congenital Heart Disease
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Peter White, Kevin Bosse, Don Corsmeier, Gloria Zender, Sara Fitzgerald-Butt, Stephanie LaHaye, Kim L. McBride, Madhumita Basu, Vidu Garg, and Jessica Bowman
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Male ,0301 basic medicine ,Candidate gene ,Heredity ,DNA Mutational Analysis ,Genome-wide association study ,Bioinformatics ,Heart Septal Defects, Atrial ,Gene Frequency ,Mutation Rate ,Risk Factors ,Databases, Genetic ,Exome ,Child ,Ductus Arteriosus, Patent ,Cells, Cultured ,Genetics (clinical) ,Exome sequencing ,Genetics ,education.field_of_study ,High-Throughput Nucleotide Sequencing ,Pedigree ,Phenotype ,Child, Preschool ,Tetralogy of Fallot ,Female ,Cardiology and Cardiovascular Medicine ,Genetic Markers ,Heart Defects, Congenital ,Adolescent ,Tolloid-Like Metalloproteinases ,Population ,Biology ,Article ,Atrial septal defects ,03 medical and health sciences ,Humans ,Computer Simulation ,Genetic Predisposition to Disease ,cardiovascular diseases ,education ,Allele frequency ,Models, Genetic ,Myosin Heavy Chains ,Infant ,GATA4 Transcription Factor ,Minor allele frequency ,030104 developmental biology ,Mutation ,Genome-Wide Association Study - Abstract
Background— Congenital heart disease (CHD) is the most common type of birth defect with family- and population-based studies supporting a strong genetic cause for CHD. The goal of this study was to determine whether a whole exome sequencing (WES) approach could identify pathogenic-segregating variants in multiplex CHD families. Methods and Results— WES was performed on 9 kindreds with familial CHD, 4 with atrial septal defects, 2 with patent ductus arteriosus, 2 with tetralogy of Fallot, and 1 with pulmonary valve dysplasia. Rare variants (GATA4 mutation in the transactivation domain, p.G115W, was identified in familial atrial septal defects and demonstrated decreased transactivation ability in vitro. A p.I263V mutation in TLL1 was identified in an atrial septal defects kindred and is predicted to affect the enzymatic functionality of TLL1. A disease-segregating splice donor site mutation in MYH11 (c.4599+1delG) was identified in familial patent ductus arteriosus and found to disrupt normal splicing of MYH11 mRNA in the affected individual. Conclusions— Our findings demonstrate the clinical utility of WES to identify causative mutations in familial CHD and demonstrate the successful use of a CHD candidate gene list to allow for a more streamlined approach enabling rapid prioritization and identification of likely pathogenic variants from large WES data sets. Clinical Trial Registration— URL: https://clinicaltrials.gov ; Unique Identifier: NCT0112048.
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- 2016
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43. CD4+ T Cells from RUPP rat model activate NK cells and cause mitochondrial oxidative stress and hypertension in normal pregnant rats
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Evangeline Deer, Tarek Ibrahim, Venkata Ramana Vaka, Owen Herrock, Lorena M. Amaral, Sara Fitzgerald, Kristin E. Reeve, Michael Franks, and Babbette LaMarca
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medicine.medical_specialty ,Endocrinology ,Chemistry ,Internal medicine ,Rat model ,Genetics ,medicine ,medicine.disease_cause ,Molecular Biology ,Biochemistry ,Oxidative stress ,Biotechnology - Published
- 2020
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44. Novel familial dilated cardiomyopathy mutation inMYL2affects the structure and function of myosin regulatory light chain
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Ana Morales, Ray E. Hershberger, Sara Fitzgerald-Butt, Danuta Szczesna-Cordary, Zhiqun Zhou, Chen-Ching Yuan, Katarzyna Kazmierczak, Jingsheng Liang, Kim L. McBride, and Wenrui Huang
- Subjects
Adult ,Cardiomyopathy, Dilated ,Male ,Myosin Light Chains ,Myosin light-chain kinase ,Protein Conformation ,DNA Mutational Analysis ,Sus scrofa ,macromolecular substances ,Biology ,Biochemistry ,Protein Structure, Secondary ,Article ,Cardiac Myosins ,Myosin ,medicine ,Animals ,Humans ,Molecular Biology ,Actin ,Adenosine Triphosphatases ,Myosin Heavy Chains ,Circular Dichroism ,Cell Biology ,musculoskeletal system ,Actins ,Recombinant Proteins ,Pedigree ,Cell biology ,MYL2 ,Amino Acid Substitution ,Mutation ,Female ,MYH7 ,medicine.symptom ,Myofibril ,Muscle contraction - Abstract
Dilated cardiomyopathy (DCM) is a disease of the myocardium characterized by left ventricular dilatation and diminished contractile function. Here we describe a novel DCM mutation in the myosin regulatory light chain (RLC), in which aspartic acid at position 94 is replaced by alanine (D94A). The mutation was identified by exome sequencing of three adult first-degree relatives who met formal criteria for idiopathic DCM. To obtain insight into the functional significance of this pathogenic MYL2 variant, we cloned and purified the human ventricular RLC wild-type (WT) and D94A mutant proteins, and performed in vitro experiments using RLC-mutant or WT-reconstituted porcine cardiac preparations. The mutation induced a reduction in the α-helical content of the RLC, and imposed intra-molecular rearrangements. The phosphorylation of RLC by Ca²⁺/calmodulin-activated myosin light chain kinase was not affected by D94A. The mutation was seen to impair binding of RLC to the myosin heavy chain, and its incorporation into RLC-depleted porcine myosin. The actin-activated ATPase activity of mutant-reconstituted porcine cardiac myosin was significantly higher compared with ATPase of wild-type. No changes in the myofibrillar ATPase-pCa relationship were observed in wild-type- or D94A-reconstituted preparations. Measurements of contractile force showed a slightly reduced maximal tension per cross-section of muscle, with no change in the calcium sensitivity of force in D94A-reconstituted skinned porcine papillary muscle strips compared with wild-type. Our data indicate that subtle structural rearrangements in the RLC molecule, followed by its impaired interaction with the myosin heavy chain, may trigger functional abnormalities contributing to the DCM phenotype.
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- 2015
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45. Assessment of Large Copy Number Variants in Patients with Apparently Isolated Congenital Left-sided Cardiac Lesions Reveals Clinically Relevant Genomic Events
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Sara Fitzgerald-Butt, Luis A. Umaña, Shaine A. Morris, Dieter Furthner, Neil A. Hanchard, Gladys Zapata, Susan D. Fernbach, Jessica Bowman, Cammon B. Arrington, Jeffrey A. Towbin, Neil E. Bowles, Siddharth K. Prakash, Seema R. Lalani, Kim L. McBride, Patricia P. Hernandez, Lisa C.A. D'Alessandro, Vidu Garg, Mojisola Poopola, Gloria Zender, John W. Belmont, and Mahshid S. Azamian
- Subjects
0301 basic medicine ,Proband ,Adult ,Heart Defects, Congenital ,Male ,Heart disease ,Adolescent ,DNA Copy Number Variations ,Genotype ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Young Adult ,Genetics ,medicine ,Humans ,Copy-number variation ,Child ,Genotyping ,Genetics (clinical) ,Genetic Association Studies ,Infant, Newborn ,Chromosome ,Infant ,Heart ,Genomics ,Middle Aged ,medicine.disease ,Phenotype ,030104 developmental biology ,Child, Preschool ,Cohort ,Female ,SNP array - Abstract
Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals.
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- 2017
46. A cohort study of multiple families with FBN1 p.R650C variant, ectopia lentis, and low but not absent risk for aortopathy
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Sara Fitzgerald-Butt, Lohith Vatti, and Kim L. McBride
- Subjects
0301 basic medicine ,Marfan syndrome ,Proband ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Genotype ,Fibrillin-1 ,Aortic Diseases ,030105 genetics & heredity ,Rate ratio ,Thoracic aortic aneurysm ,Polymorphism, Single Nucleotide ,Ectopia Lentis ,Marfan Syndrome ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Genetics ,medicine ,Humans ,Ectopia lentis ,Child ,Genetics (clinical) ,Aged ,business.industry ,Middle Aged ,medicine.disease ,Pedigree ,Phenotype ,Child, Preschool ,Cohort ,Mutation ,030221 ophthalmology & optometry ,Cardiology ,Female ,Age of onset ,business ,Cohort study - Abstract
Marfan syndrome is a multisystem disease with cardiovascular, ophthalmologic, and skeletal features. Diagnosis is made clinically with emphasis on presence of aortic root dilation and ectopia lentis (EL). Most individuals meeting these criteria have a pathogenic variant in FBN1, usually unique or observed rarely. Individuals with EL alone may also have FBN1 pathogenic variants, and the risk for aortic disease is not well known. We identified a unique cohort of 31 individuals (mean age 29, range 2–78) from nine families ascertained by a proband with EL alone, who had the same FBN1 p.R650C variant. Comparison was made to individuals with Marfan syndrome (n = 103 from 97 families) at our institution. Those with the p.R650C variant had few skeletal features of Marfan syndrome. Age of onset of EL was later compared to others with cysteine variant changes. Aortic root dilation occurred in 4/16 (25%) of the p.R650C group versus 71/83 (86%) in the comparator group (p
- Published
- 2017
47. Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve
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Vidu Garg, Sara Fitzgerald-Butt, May Ling Mah, Kim L. McBride, John P. Kovalchin, Jessica Bowman, and Holly Nadorlik
- Subjects
Aortic valve ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Aortic Diseases ,Heart Valve Diseases ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,Article ,03 medical and health sciences ,Aortic aneurysm ,Young Adult ,0302 clinical medicine ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,Risk Factors ,Internal medicine ,medicine.artery ,Ascending aorta ,medicine ,Humans ,Mass Screening ,030212 general & internal medicine ,Longitudinal Studies ,Family history ,Child ,Aorta ,business.industry ,medicine.disease ,Cardiac surgery ,medicine.anatomical_structure ,Echocardiography ,Aortic Valve ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Bicuspid aortic valve (BAV) is the most common type of congenital heart defect (CHD) and is associated with clinically significant cardiovascular complications including valve calcification and ascending aortopathy (AscAo), predominantly occurring in adulthood. While a limited number of genetic etiologies for BAV have been defined, family members of affected individuals display BAV along with other left-sided CHD. This has led to guidelines from the American Heart Association and American College of Cardiology that recommend echocardiographic screening of first-degree relatives of affected adults. While potentially beneficial in adults, the yield of such screening in children is unknown. The purpose of this study was to investigate a cohort of children with familial BAV to determine the frequency of development of AscAo, and to identify risk factors that contribute to abnormal aortic growth. Echocardiograms over a 10-year follow-up period were reviewed on 26 patients with familial BAV [22 male, 4 female; 22 with isolated BAV, 6 with BAV and aortic coarctation (CoA)]. All had a family history of CHD and were recruited from 2005 to 2010 as part of a genetics research study. Four aortic segments (annulus, root, sinotubular junction, ascending aorta) on parasternal long-axis echocardiographic images were measured by a single observer. The mean age at first echocardiogram was 7.1 ± 5.5 and that was 13.8 ± 6.2 years at the last echocardiogram. Only patients with > 2 echocardiograms in the 10-year period were included. Z score measurements of the aorta were plotted over time and based on these the cohort was divided into two groups: Group 1 (abnormal)—Z score for any segment > 2 or a change in Z score > 2 over follow-up; Group 2 (normal)—Z score
- Published
- 2017
48. Genetic knowledge and attitudes of parents of children with congenital heart defects
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Deena J. Chisolm, Jennifer Klima, Kim L. McBride, Kelly J. Kelleher, and Sara Fitzgerald-Butt
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Heart Defects, Congenital ,Male ,Parents ,Health Knowledge, Attitudes, Practice ,Disease ,Article ,Health care ,Genetics ,Clinical genetic ,medicine ,Humans ,Genetic Testing ,Child ,Genetics (clinical) ,Demography ,Ohio ,Genetic testing ,Models, Statistical ,Social discrimination ,medicine.diagnostic_test ,business.industry ,Educational attainment ,Socioeconomic Factors ,Educational Status ,Household income ,Female ,business ,Pediatric cardiology - Abstract
Clinical genetic testing for specific isolated congenital heart defects (CHD) is becoming standard of care in pediatric cardiology practice. Both genetic knowledge and attitudes toward genetic testing are associated with an increased utilization of genetic testing, but these factors have not been evaluated in parents of children with CHD. We mailed a survey to measure the demographics, genetic knowledge, and attitudes towards genetic testing of parents of children with CHD who previously consented to participate in a separate research study of the genetic etiology of left ventricular outflow tract malformations (LVOT). Of the 378 eligible families, 190 (50%) returned surveys with both parents completing surveys in 97 (51%) families, resulting in 287 participants. Genetic knowledge was assessed on an adapted measure on which the mean percent correct was 73.8%. Educational attainment and household income were directly and significantly associated with genetic knowledge (P 0.001). Attitudes about the health effects of genetic testing were favorable with at least 57% agreeing that genetic testing would be used for managing health care and finding cures for disease. Conversely, a minority of participants found it likely that genetic testing would be used for insurance (up to 39.9%), employment (15.8%), or racial/social discrimination (up to 11.2%). Parents of younger children were less likely to endorse employment or racial/social discrimination. Genetic knowledge was not correlated with specific attitudes. Among parents of children with CHD, genetic knowledge was directly associated with household income and education, but additional research is necessary to determine what factors influence attitudes towards genetic testing.
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- 2014
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49. Rare GATA5 sequence variants identified in individuals with bicuspid aortic valve
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Gloria Zender, Stephanie LaHaye, Vidu Garg, Sara Fitzgerald-Butt, Sheng-Wei Chang, Kim L. McBride, and Elizabeth M. Bonachea
- Subjects
Male ,Aortic valve ,Nonsynonymous substitution ,Heart disease ,GATA5 Transcription Factor ,Immunoblotting ,Molecular Sequence Data ,Heart Valve Diseases ,Mutation, Missense ,Article ,Cohort Studies ,symbols.namesake ,Bicuspid aortic valve ,Bicuspid Aortic Valve Disease ,Genetic etiology ,medicine ,Humans ,DNA Primers ,Ohio ,Sequence (medicine) ,Sanger sequencing ,Genetics ,Transcriptional activity ,Base Sequence ,business.industry ,Genetic Variation ,Sequence Analysis, DNA ,medicine.disease ,Phenotype ,medicine.anatomical_structure ,Aortic Valve ,Pediatrics, Perinatology and Child Health ,cardiovascular system ,symbols ,Female ,business - Abstract
Bicuspid aortic valve (BAV) is the most common type of congenital heart disease (CHD) and has a proposed genetic etiology. BAV is categorized by cusp fusion, with right-left (R-L) cusp fusion being associated with additional CHD, and right-noncoronary cusp (R-NC) fusion being associated with aortic valve dysfunction. Loss of murine Gata5, which encodes a cardiac transcription factor, results in a partially penetrant R-NC BAV, and we hypothesize that mutations in GATA5 are associated with R-NC BAV in humans. A cohort of 78 BAV patients (50 with isolated BAV and 28 with associated aortic coarctation) was analyzed using Sanger sequencing to identify GATA5 sequence variants. Biochemical assays were performed to identify functional deficits of identified sequence variants. We identified two rare heterozygous nonsynonymous variants, p.Gln3Arg and p.Leu233Pro, for a frequency of 2.6% (2/78). Both individuals with nonsynonymous variants had BAV and aortic coarctation, one R-L and one R-NC subtype. Of the nonsynonymous variants, only p.Gln3Arg demonstrated decreased transcriptional activity in vitro. Rare sequence variants in GATA5 are associated with human BAV. Our findings suggest a genotype–phenotype correlation in regards to associated CHD but not cusp fusion.
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- 2014
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50. Understanding of informed consent by parents of children enrolled in a genetic biobank
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Sara Fitzgerald-Butt, Kelly J. Kelleher, Amy K. Ferketich, Jennifer Klima, Kim L. McBride, R. Dawn Comstock, and Deena J. Chisolm
- Subjects
Adult ,Male ,Parents ,Health Knowledge, Attitudes, Practice ,medicine.medical_specialty ,media_common.quotation_subject ,Cardiovascular Abnormalities ,Informed consent ,Genetic etiology ,medicine ,Humans ,Parental Consent ,Quality (business) ,Generalized estimating equation ,Genetics (clinical) ,Biological Specimen Banks ,media_common ,Informed Consent ,business.industry ,Medical decision making ,Biobank ,Family medicine ,Research studies ,Female ,Cardiovascular malformations ,business - Abstract
Prior research suggests that parents undervalue long-term risks associated with their children’s participation in research studies. The primary aim of this study was to evaluate parental understanding of informed consent for a pediatric biobanking study. The study population included parents who provided consent for their child to participate in a study examining the genetic etiology of congenital cardiovascular malformations. Informed consent understanding was measured by adapting the Quality of Informed Consent assessment to our study. We evaluated possible predictors of individual Quality of Informed Consent items using generalized estimating equations. A total of 252 individuals representing 188 families completed the study. The Quality of Informed Consent items best understood by parents included consent to participate in research, the main purpose of the study, and the possibility of no direct benefit. The items least understood by parents were those involving the indefinite storage of DNA, the possible risks of participation, and the fact that the study was not intended to treat their child’s heart defect. Parent age and medical decision making by one versus both parents were frequent predictors of individual Quality of Informed Consent items. Parents overestimate personal benefit and underestimate the risks associated with their child’s participation in a biobanking study. Genet Med 16 2, 141–148.
- Published
- 2014
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