journal
MENU ▼
Read by QxMD icon Read
search

Genetics in Medicine: Official Journal of the American College of Medical Genetics

journal
https://www.readbyqxmd.com/read/30008476/role-of-mdh2-pathogenic-variant-in-pheochromocytoma-and-paraganglioma-patients
#1
Bruna Calsina, Maria Currás-Freixes, Alexandre Buffet, Tirso Pons, Laura Contreras, Rocío Letón, Iñaki Comino-Méndez, Laura Remacha, María Calatayud, Berta Obispo, Antoine Martin, Regis Cohen, Susan Richter, Judith Balmaña, Esther Korpershoek, Elena Rapizzi, Timo Deutschbein, Laurent Vroonen, Judith Favier, Ronald R de Krijger, Martin Fassnacht, Felix Beuschlein, Henri J Timmers, Graeme Eisenhofer, Massimo Mannelli, Karel Pacak, Jorgina Satrústegui, Cristina Rodríguez-Antona, Laurence Amar, Alberto Cascón, Nicole Dölker, Anne-Paule Gimenez-Roqueplo, Mercedes Robledo
PURPOSE: MDH2 (malate dehydrogenase 2) has recently been proposed as a novel potential pheochromocytoma/paraganglioma (PPGL) susceptibility gene, but its role in the disease has not been addressed. This study aimed to determine the prevalence of MDH2 pathogenic variants among PPGL patients and determine the associated phenotype. METHODS: Eight hundred thirty patients with PPGLs, negative for the main PPGL driver genes, were included in the study. Interpretation of variants of unknown significance (VUS) was performed using an algorithm based on 20 computational predictions, by implementing cell-based enzymatic and immunofluorescence assays, and/or by using a molecular dynamics simulation approach...
July 16, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/30008475/clinical-genome-sequencing-in-an-unbiased-pediatric-cohort
#2
Isabelle Thiffault, Emily Farrow, Lee Zellmer, Courtney Berrios, Neil Miller, Margaret Gibson, Raymond Caylor, Janda Jenkins, Deb Faller, Sarah Soden, Carol Saunders
PURPOSE: We report for the first time, the use of clinical genome sequencing (GS) in an unbiased pediatric cohort. We describe the clinical validation, patient metrics, ordering patterns, results, reimbursement, and physician retrieval of results for the first consecutive 80 cases. METHODS: Clinical GS was performed for both inpatients and outpatients undergoing etiologic evaluations. Results were reported in the electronic medical record. Evidence of report retrieval by clinicians and whether interpretation was concordant with laboratory report was obtained through retrospective chart review...
July 16, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997393/phrank-measures-phenotype-sets-similarity-to-greatly-improve-mendelian-diagnostic-disease-prioritization
#3
Karthik A Jagadeesh, Johannes Birgmeier, Harendra Guturu, Cole A Deisseroth, Aaron M Wenger, Jonathan A Bernstein, Gill Bejerano
PURPOSE: Exome sequencing and diagnosis is beginning to spread across the medical establishment. The most time-consuming part of genome-based diagnosis is the manual step of matching the potentially long list of patient candidate genes to patient phenotypes to identify the causative disease. METHODS: We introduce Phrank (for phenotype ranking), an information theory-inspired method that utilizes a Bayesian network to prioritize candidate diseases or genes, as a stand-alone module that can be run with any underlying knowledgebase and any variant filtering scheme...
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997392/direct-to-consumer-raw-genetic-data-and-third-party-interpretation-services-more-burden-than-bargain
#4
Tia Moscarello, Brittney Murray, Chloe M Reuter, Erin Demo
No abstract text is available yet for this article.
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997391/exome-sequencing-in-congenital-ataxia-identifies-two-new-candidate-genes-and-highlights-a-pathophysiological-link-between-some-congenital-ataxias-and-early-infantile-epileptic-encephalopathies
#5
Stéphanie Valence, Emmanuelle Cochet, Christelle Rougeot, Catherine Garel, Sandra Chantot-Bastaraud, Elodie Lainey, Alexandra Afenjar, Marie-Anne Barthez, Nathalie Bednarek, Diane Doummar, Laurence Faivre, Cyril Goizet, Damien Haye, Bénédicte Heron, Isabelle Kemlin, Didier Lacombe, Mathieu Milh, Marie-Laure Moutard, Florence Riant, Stéphanie Robin, Agathe Roubertie, Pierre Sarda, Annick Toutain, Laurent Villard, Dorothée Ville, Thierry Billette de Villemeur, Diana Rodriguez, Lydie Burglen
PURPOSE: To investigate the genetic basis of congenital ataxias (CAs), a unique group of cerebellar ataxias with a nonprogressive course, in 20 patients from consanguineous families, and to identify new CA genes. METHODS: Singleton -exome sequencing on these 20 well-clinically characterized CA patients. We first checked for rare homozygous pathogenic variants, then, for variants from a list of genes known to be associated with CA or very early-onset ataxia, regardless of their mode of inheritance...
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997390/allelic-phenotype-values-a-model-for-genotype-based-phenotype-prediction-in-phenylketonuria
#6
Sven F Garbade, Nan Shen, Nastassja Himmelreich, Dorothea Haas, Friedrich K Trefz, Georg F Hoffmann, Peter Burgard, Nenad Blau
PURPOSE: The nature of phenylalanine hydroxylase (PAH) variants determines residual enzyme activity, which modifies the clinical phenotype in phenylketonuria (PKU). We exploited the statistical power of a large genotype database to determine the relationship between genotype and phenotype in PKU. METHODS: A total of 9336 PKU patients with 2589 different genotypes, carrying 588 variants, were investigated using an allelic phenotype value (APV) algorithm. RESULTS: We identified 251 0-variants encoding inactive PAH, and assigned APVs (0 = classic PKU; 5 = mild PKU; 10 = mild hyperphenylalaninaemia) to 88 variants in PAH-functional hemizygous patients...
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997389/health-behaviors-among-unaffected-participants-following-receipt-of-variants-of-uncertain-significance-in-cardiomyopathy-associated-genes
#7
Ilana M Miller, Katie L Lewis, Tokunbor A Lawal, David Ng, Jennifer J Johnston, Barbara B Biesecker, Leslie G Biesecker
PURPOSE: Studies on returning variants of uncertain significance (VUS) results have predominantly included patients with a personal or family history of cancer and cancer-associated gene VUS. This study examined health behaviors among participants with cardiomyopathy-associated gene VUS, but without a personal history of cardiomyopathy. METHODS: Sixty-eight eligible participants without apparent cardiomyopathy but with VUS in cardiomyopathy-associated genes completed a survey of health behaviors, disclosure, distress, uncertainty, positive experiences, decisional conflict, and perceived value...
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997388/private-payer-coverage-policies-for-exome-sequencing-es-in-pediatric-patients-trends-over-time-and-analysis-of-evidence-cited
#8
Michael P Douglas, Stephanie L Parker, Julia R Trosman, Anne M Slavotinek, Kathryn A Phillips
PURPOSE: Exome sequencing (ES) is being adopted for neurodevelopmental disorders in pediatric patients. However, little is known about current coverage policies or the evidence cited supporting these policies. Our study is the first in-depth review of private payer ES coverage policies for pediatric patients with neurodevelopmental disorders. METHODS: We reviewed private payer coverage policies and examined evidence cited in the policies of the 15 largest payers in 2017, and trends in coverage policies and evidence cited (2015-2017) for the five largest payers...
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997387/opportunities-to-implement-a-sustainable-genomic-medicine-program-lessons-learned-from-the-ignite-network
#9
Kenneth D Levy, Kathryn Blake, Colette Fletcher-Hoppe, James Franciosi, Diasuke Goto, James K Hicks, Ann M Holmes, Sri Harsha Kanuri, Ebony B Madden, Michael D Musty, Lori Orlando, Victoria M Pratt, Michelle Ramos, Ryanne Wu, Geoffrey Ginsburg
PURPOSE: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice...
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29997386/micrornas-as-biomarkers-in-pompe-disease
#10
Antonietta Tarallo, Annamaria Carissimo, Francesca Gatto, Edoardo Nusco, Antonio Toscano, Olimpia Musumeci, Marcella Coletta, Marianthi Karali, Emma Acampora, Carla Damiano, Nadia Minopoli, Simona Fecarotta, Roberto Della Casa, Tiziana Mongini, Liliana Vercelli, Lucio Santoro, Lucia Ruggiero, Federica Deodato, Roberta Taurisano, Bruno Bembi, Andrea Dardis, Sandro Banfi, W W Pim Pijnappel, Ans T van der Ploeg, Giancarlo Parenti
PURPOSE: We studied microRNAs as potential biomarkers for Pompe disease. METHODS: We analyzed microRNA expression by small RNA-seq in tissues from the disease murine model at two different ages (3 and 9 months), and in plasma from Pompe patients. RESULTS: In the mouse model we found 211 microRNAs that were differentially expressed in gastrocnemii and 66 in heart, with a different pattern of expression at different ages. In a preliminary analysis in plasma from six patients 55 microRNAs were differentially expressed...
July 12, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29988080/the-functional-impact-of-variants-of-uncertain-significance-in-brca2
#11
Romy L S Mesman, Fabienne M G R Calléja, Giel Hendriks, Bruno Morolli, Branislav Misovic, Peter Devilee, Christi J van Asperen, Harry Vrieling, Maaike P G Vreeswijk
PURPOSE: Genetic testing has uncovered large numbers of variants in the BRCA2 gene for which the clinical significance is unclear. Cancer risk prediction of these variants of uncertain significance (VUS) can be improved by reliable assessment of the extent of impairment of the tumor suppressor function(s) of BRCA2. METHODS: Here, we evaluated the performance of the mouse embryonic stem cell (mESC)-based functional assay on an extensive set of BRCA2 missense variants...
July 10, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29988079/navigating-the-nuances-of-clinical-sequence-variant-interpretation-in-mendelian-disease
#12
REVIEW
Natasha T Strande, Sarah E Brnich, Tamara S Roman, Jonathan S Berg
Understanding clinical genetic test results in the era of next-generation sequencing has become increasingly complex, necessitating clear and thorough guidelines for sequence variant interpretation. To meet this need the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for a systematic approach for sequence variant interpretation in 2015. This framework is intended to be adaptable to any Mendelian condition, promoting transparency and consistency in variant interpretation, yet its comprehensive nature yields important challenges and caveats that end users must understand...
July 10, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29988078/accelerating-evidence-gathering-and-approval-of-precision-medicine-therapies-the-fda-takes-aim-at-rare-mutations
#13
Amalia M Issa, Adrian Thorogood, Yann Joly, Bartha M Knoppers
No abstract text is available yet for this article.
July 10, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29988077/landscape-of-pathogenic-variations-in-a-panel-of-34-genes-and-cancer-risk-estimation-from-5131-hboc-families
#14
Laurent Castéra, Valentin Harter, Etienne Muller, Sophie Krieger, Nicolas Goardon, Agathe Ricou, Antoine Rousselin, Germain Paimparay, Angelina Legros, Olivia Bruet, Céline Quesnelle, Florian Domin, Chankannira San, Baptiste Brault, Robin Fouillet, Caroline Abadie, Odile Béra, Pascaline Berthet, Thierry Frébourg, Dominique Vaur
PURPOSE: Integration of gene panels in the diagnosis of hereditary breast and ovarian cancer (HBOC) requires a careful evaluation of the risk associated with pathogenic or likely pathogenic variants (PVs) detected in each gene. Here we analyzed 34 genes in 5131 suspected HBOC index cases by next-generation sequencing. METHODS: Using the Exome Aggregation Consortium data sets plus 571 individuals from the French Exome Project, we simulated the probability that an individual from the Exome Aggregation Consortium carries a PV and compared it to the estimated frequency within the HBOC population...
July 10, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29976988/developing-a-conceptual-reproducible-rubric-based-approach-to-consent-and-result-disclosure-for-genetic-testing-by-clinicians-with-minimal-genetics-background
#15
Kelly E Ormond, Miranda L G Hallquist, Adam H Buchanan, Danielle Dondanville, Mildred K Cho, Maureen Smith, Myra Roche, Kyle B Brothers, Curtis R Coughlin, Laura Hercher, Louanne Hudgins, Seema Jamal, Howard P Levy, Misha Raskin, Melissa Stosic, Wendy Uhlmann, Karen E Wain, Erin Currey, W Andrew Faucett
PURPOSE: In response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Disclosure Recommendations (CADRe) Workgroup of the Clinical Genome Resource (ClinGen; clinicalgenome.org ) developed guidance to facilitate communication about genetic testing and efficiently improve the patient experience. Considering ethical, legal, and social implications, and medical factors, CADRe developed and pilot tested two rubrics addressing consent for genetic testing and results disclosure...
July 6, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29970926/normative-and-conceptual-elsi-research-what-it-is-and-why-it-s-important
#16
Lisa S Parker, Pamela L Sankar, Joy Boyer, J D Jean McEwen, David Kaufman
The Ethical, Legal, and Social Implications (ELSI) Research Program of the National Human Genome Research Institute sponsors research examining ethical, legal, and social issues arising in the context of genetics/genomics. The ELSI Program endorses an understanding of research not as the sole province of empirical study, but instead as systematic study or inquiry, of which there are many types and methods. ELSI research employs both empirical and nonempirical methods. Because the latter remain relatively unfamiliar to biomedical and translational scientists, this paper seeks to elucidate the relationship between empirical and nonempirical methods in ELSI research...
July 4, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29970925/growth-characteristics-in-individuals-with-osteogenesis-imperfecta-in-north-america-results-from-a-multicenter-study
#17
Mahim Jain, Allison Tam, Jay R Shapiro, Robert D Steiner, Peter A Smith, Michael B Bober, Tracy Hart, David Cuthbertson, Jeff Krischer, Mary Mullins, Sunil Bellur, Peter H Byers, Melanie Pepin, Michaela Durigova, Francis H Glorieux, Frank Rauch, Brendan Lee, V Reid Sutton, Sandesh C S Nagamani
PURPOSE: Osteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI. METHODS: Using data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves...
July 4, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29961769/population-genomics-in-south-east-asia-captures-unexpectedly-high-carrier-frequency-for-treatable-inherited-disorders
#18
Yasmin Bylstra, Jyn Ling Kuan, Weng Khong Lim, Jaydutt Digambar Bhalshankar, Jing Xian Teo, Sonia Davila, Bin Tean Teh, Steve Rozen, Ene-Choo Tan, Wendy Kein Meng Liew, Khung Keong Yeo, Patrick Tan, Seang Mei Saw, Ching-Yu Cheng, Stuart Cook, Roger Foo, Saumya Shekhar Jamuar
PURPOSE: Genomic studies have demonstrated the necessity of ethnicity-specific population data to ascertain variant pathogenicity for disease diagnosis and treatment. This study examined the carrier prevalence of treatable inherited disorders (TIDs), where early diagnosis of at-risk offspring can significantly improve clinical outcomes. METHODS: Existing exome/ genome sequencing data of 831 Singaporeans were aggregated and examined for disease causing variants in 104 genes associated with 80 TIDs...
July 2, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29961768/germline-cancer-susceptibility-gene-variants-somatic-second-hits-and-survival-outcomes-in-patients-with-resected-pancreatic-cancer
#19
Matthew B Yurgelun, Anu B Chittenden, Vicente Morales-Oyarvide, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Zhi Rong Qian, Marisa W Welch, Lauren K Brais, Annacarolina Da Silva, Justin L Bui, Chen Yuan, Tingting Li, Wanwan Li, Atsuhiro Masuda, Mancang Gu, Andrea J Bullock, Daniel T Chang, Thomas E Clancy, David C Linehan, Jennifer J Findeis-Hosey, Leona A Doyle, Aaron R Thorner, Matthew D Ducar, Bruce M Wollison, Natalia Khalaf, Kimberly Perez, Sapna Syngal, Andrew J Aguirre, William C Hahn, Matthew L Meyerson, Charles S Fuchs, Shuji Ogino, Jason L Hornick, Aram F Hezel, Albert C Koong, Jonathan A Nowak, Brian M Wolpin
PURPOSE: Germline variants in double-strand DNA damage repair (dsDDR) genes (e.g., BRCA1/2) predispose to pancreatic adenocarcinoma (PDAC) and may predict sensitivity to platinum-based chemotherapy and poly(ADP) ribose polymerase (PARP) inhibitors. We sought to determine the prevalence and significance of germline cancer susceptibility gene variants in PDAC with paired somatic and survival analyses. METHODS: Using a customized next-generation sequencing panel, germline/somatic DNA was analyzed from 289 patients with resected PDAC ascertained without preselection for high-risk features (e...
July 2, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29961767/genome-sequencing-as-a-first-line-genetic-test-in-familial-dilated-cardiomyopathy
#20
Andre E Minoche, Claire Horvat, Renee Johnson, Velimir Gayevskiy, Sarah U Morton, Alexander P Drew, Kerhan Woo, Aaron L Statham, Ben Lundie, Richard D Bagnall, Jodie Ingles, Christopher Semsarian, J G Seidman, Christine E Seidman, Marcel E Dinger, Mark J Cowley, Diane Fatkin
PURPOSE: We evaluated genome sequencing (GS) as an alternative to multigene panel sequencing (PS) for genetic testing in dilated cardiomyopathy (DCM). METHODS: Forty-two patients with familial DCM underwent PS and GS, and detection rates of rare single-nucleotide variants and small insertions/deletions in panel genes were compared. Loss-of-function variants in 406 cardiac-enriched genes were evaluated, and an assessment of structural variation was performed. RESULTS: GS provided broader and more uniform coverage than PS, with high concordance for rare variant detection in panel genes...
July 2, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
journal
journal
33134
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"