Article
Genetics & Heredity
Monica H. Wojcik, Maya C. del Rosario, Pankaj B. Agrawal
Summary: A survey of neonatologists across the United States revealed that while most acknowledge the importance of genetic testing for their patients, availability of genetic consultations and exome or genome sequencing in NICUs is not always adequate.
GENETICS IN MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Hongchun Xiong, Huijun Guo, Meiyu Fu, Yongdun Xie, Linshu Zhao, Jiayu Gu, Shirong Zhao, Yuping Ding, Qidi Du, Jiazi Zhang, Lin Qiu, Xiaomei Xie, Libin Zhou, Zhongxu Chen, Luxiang Liu
Summary: To overcome the challenge posed by the large genome of hexaploid wheat, researchers generated a wheat mutant database through whole-exome sequencing. The database contains a diverse array of genetic variations induced by different mutagenesis methods, providing a valuable resource for functional genomics studies in wheat.
PLANT BIOTECHNOLOGY JOURNAL
(2023)
Article
Oncology
Chenyue Zhang, Kai Wang, Wenjie Liu, Jiamao Lin, Zhenxiang Li, Hui Wang, Chenglong Zhao, Yanhua Chen, Shuangxiu Wu, Airong Yang, Jiayan Wu, Haiyong Wang
Summary: This study describes the genomic and immunological landscape of Chinese mucinous pulmonary adenocarcinoma (MPA) and compares it with classical lung adenocarcinoma (LUAD). It is found that MPA has distinct genomic alterations and a more complex genomic profile compared to LUAD. Mutations in specific pathways are associated with survival outcomes, and mutations in immune-related genes also affect prognosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Clinical Neurology
Yuhan Xie, Julian N. Acosta, Yixuan Ye, Zachariah S. Demarais, Carolyn J. Conlon, Ming Chen, Hongyu Zhao, Guido J. Falcone
Summary: This study used whole-exome sequencing data from 152,058 UK Biobank participants and identified a significant association between a rare genetic variant at CYP2R1 and the risk of ischemic stroke (IS). Validation analyses further confirmed this association in other cohorts and neuroimaging traits.
Article
Rheumatology
Yiming Luo, Marcela A. Ferrada, Keith A. Sikora, Cameron Rankin, Hugh D. Alessi, Daniel L. Kastner, Zuoming Deng, Mengqi Zhang, Peter A. Merkel, Virginia B. Kraus, Andrew S. Allen, Peter C. Grayson
Summary: This study suggests that rare variants in the DCBLD2 gene may play a role in the development of RP. These findings should be further validated in a larger sample and supported by functional experiments.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Health Care Sciences & Services
Min-Rou Lin, Che-Mai Chang, Jafit Ting, Jan-Gowth Chang, Wan-Hsuan Chou, Kuei-Jung Huang, Gloria Cheng, Hsiao-Huang Chang, Wei-Chiao Chang
Summary: Marfan syndrome is a rare disease that affects multiple organ systems. This study identified potential pathogenic genes associated with MFS using whole exome sequencing in a Taiwan cohort, and also discovered novel candidate genes. The findings contribute to a better understanding of the pathogenesis of MFS.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Medicine, General & Internal
Su-Jung Park, Narae Lee, Seong-Hee Jeong, Mun-Hui Jeong, Shin-Yun Byun, Kyung-Hee Park
Summary: The prevalence of genetic causes in SGA infants without known risk factors was 22%, and targeted-panel sequencing or whole-exome sequencing was effective in diagnosing the etiology of SGA infants without a known cause.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Public, Environmental & Occupational Health
Temis Maria Felix, Carolina Fischinger Moura de Souza, Joao Bosco Oliveira, Mariana Rico-Restrepo, Edmar Zanoteli, Mayana Zatz, Roberto Giugliani
Summary: Early diagnosis of genetic rare diseases is essential in Brazil, where a large number of people live with these conditions. The use of advanced testing techniques can speed up diagnosis, reduce unnecessary procedures and treatments, and decrease healthcare costs.
INTERNATIONAL JOURNAL FOR EQUITY IN HEALTH
(2023)
Article
Allergy
Craig D. Platt, Fatima Zaman, Wayne Bainter, Kelsey Stafstrom, Abuarahman Almutairi, Margot Reigle, Sabrina Weeks, Raif S. Geha, Janet Chou
Summary: This study compared targeted next-generation sequencing with whole-exome sequencing in a global population of patients with primary immunodeficiency. The results showed that whole-exome sequencing had advantages in diagnostic yield, cost savings, and the potential for identification of novel diseases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Hosneara Akter, Mohammad Shahnoor Hossain, Nushrat Jahan Dity, Md. Atikur Rahaman, K. M. Furkan Uddin, Nasna Nassir, Ghausia Begum, Reem Abdel Hameid, Muhammad Sougatul Islam, Tahrima Arman Tusty, Mohammad Basiruzzaman, Shaoli Sarkar, Mazharul Islam, Sharmin Jahan, Elaine T. Lim, Marc Woodbury-Smith, Dimitri James Stavropoulos, Darren D. O'Rielly, Bakhrom K. Berdeiv, A. H. M. Nurun Nabi, Mohammed Nazmul Ahsan, Stephen W. Scherer, Mohammed Uddin
Summary: Rare genetic diseases affect a significant number of individuals worldwide, and whole-exome sequencing in this study identified pathogenic variants in five children from Bangladesh. Variants in disease-associated genes were found, adding to the genetic heterogeneity of rare genetic diseases. The study provides insights into the genetic profile of rare genetic diseases in the Bangladesh population.
NPJ GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Yvonne Poker, Sandra von Hardenberg, Winfried Hofmann, Ming Tang, Ulrich Baumann, Nicolaus Schwerk, Martin Wetzke, Viola Lindenthal, Bernd Auber, Brigitte Schlegelberger, Hagen Ott, Philipp von Bismarck, Dorothee Viemann, Frank Dressler, Christian Klemann, Anke Katharina Bergmann
Summary: Monogenic autoinflammatory diseases (AID) are a growing group of innate immune system defects causing systemic inflammation. This study evaluated different diagnostic strategies, including virtual gene panels and whole exome sequencing (WES), for pediatric patients with suspected monogenic AID. The results showed that analyzing virtual gene panels had a higher diagnostic yield compared to WES analysis, suggesting that WES as a first-tier diagnostic analysis is of limited benefit for monogenic AID.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Adeline Germain, Jeanne-Marie Perotin, Gonzague Delepine, Myriam Polette, Gaetan Deslee, Valerian Dormoy
Summary: A comparative whole-exome sequencing analysis was performed on bronchial epithelia from COPD and non-COPD subjects, revealing genetic alterations and copy number variations in remodelled epithelia, mainly in COPD patients. Functional analysis highlighted cilia-associated processes, indicating a greater genetic alteration in remodelled epithelia.
Article
Medicine, Research & Experimental
Hong Lian, Shen Song, Wenzheng Chen, Anteng Shi, Haobin Jiang, Shengshou Hu
Summary: This study aimed to characterize the genetic basis of dilated cardiomyopathy (DCM) in heart transplantation (HTx) patients in the Chinese population. The results showed that TTN and FLNC genes harbored a significant number of pathogenic and likely pathogenic variants, and FLNC truncation could lead to severe clinical symptoms in DCM patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Lihua Chen, Jiajia Li, Xiaohua Wu, Zhong Zheng
Summary: The study aimed to explore the genomic abnormalities associated with uterine leiomyosarcoma (uLMS) and identify potential therapeutic targets. Analysis revealed mutational heterogeneity of uLMS and highlighted the amplification of the SHARPIN gene as a candidate oncogene in uLMS.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Emily Alsentzer, Samuel Finlayson, Michelle Li, Shilpa Kobren, Isaac Kohane
Summary: Rare Mendelian disorders present a diagnostic challenge, and researchers have developed a computational pipeline to simulate realistic clinical datasets for evaluating and improving diagnostic tools.
NATURE COMMUNICATIONS
(2023)
Article
Clinical Neurology
Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D. Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K. G. Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C. Spillmann, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J. Bellen, Simon Edvardson, Florian Eichler, Teresa M. Dunn
Summary: Sphingolipids, abundant in myelin membranes, are crucial for the structural and signalling functions in the mammalian nervous system. Serine palmitoyltransferase (SPTSSA) is the enzyme responsible for the rate-limiting reaction in sphingolipid synthesis and its activity is tightly regulated by ORMDL proteins. Excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase was found to be responsible for defects in early brain development and function. SRivastava et al. identified SPTSSA variants that disrupt ORMDL-mediated regulation of SPT, leading to hereditary spastic paraplegia.
Article
Genetics & Heredity
Christina Y. Miyake, Erica J. Lay, Claudia Soler-Alfonso, Kevin E. Glinton, Kimberly M. Houck, Mustafa Tosur, Nancy E. Moran, Sara B. Stephens, Fernando Scaglia, Taylor S. Howard, Jeffrey J. Kim, Tam Dam Pham, Santiago O. Valdes, Na Li, Chaya N. Murali, Lilei Zhang, Maina Kava, Deane Yim, Cheyenne Beach, Gregory Webster, Leonardo Liberman, Christopher M. Janson, Prince J. Kannankeril, Samantha Baxter, Moriel Singer-Berk, Jordan Wood, Samuel J. Mackenzie, Michael Sacher, Lina Ghaloul-Gonzalez, Claudia Pedroza, Shaine A. Morris, Saad A. Ehsan, Mahshid S. Azamian, Seema R. Lalani
Summary: This study provides a comprehensive review of the natural history of TANGO2 deficiency disorder and important observational data suggesting that B-complex or multivitamins may prevent metabolic crises.
GENETICS IN MEDICINE
(2023)
Article
Biochemical Research Methods
David J. Degnan, Kelly G. Stratton, Rachel Richardson, Daniel Claborne, Evan A. Martin, Nathan A. Johnson, Damon Leach, Bobbie-Jo M. Webb-Robertson, Lisa M. Bramer
Summary: The pmartR package is designed for QC and analysis of mass spectrometry data, specifically for proteomic, metabolomic, and lipidomic datasets. It has been expanded to include nuclear magnetic resonance metabolomic data and transcriptomic data analysis using DESeq2, edgeR, and limma-voom R packages. The package also offers improved statistics and visualization capabilities, including support for paired data and integration with the trelliscopejs R package.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Genetics & Heredity
Rebecca C. Spillmann, Queenie K. -G. Tan, Chloe Reuter, Kelly Schoch, Jennefer Kohler, Devon Bonner, Diane Zastrow, Anna Alkelai, Evan Baugh, Heidi Cope, Shruti Marwaha, Matthew T. Wheeler, Jonathan A. Bernstein, Vandana Shashi
Summary: Next-generation sequencing has transformed the diagnostic process for rare/ultrarare conditions. However, the diagnosis rates vary depending on the analytical pipelines. A dual analysis approach combining the expertise of core laboratories and clinical sites can improve both variant detection and prioritization.
GENETICS IN MEDICINE
(2023)
Editorial Material
Oncology
Paul Graham Fisher
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biology
Agustin Leonardo Lujan, Ombretta Foresti, Conor Sugden, Nathalie Brouwers, Alex Mateo Farre, Alessio Vignoli, Mahshid Azamian, Alicia Turner, Jose Wojnacki, Vivek Malhotra, Suzanne R. Pfeffer
Summary: TANGO2 primarily localizes to mitochondria and partially to mitochondria sites adjacent to lipid droplets and the endoplasmic reticulum. Cells lacking TANGO2 exhibit enlarged lipid droplets, with an increase in lysophosphatidic acid (LPA) and a decrease in its biosynthetic precursor phosphatidic acid (PA) observed through quantitative lipidomics. Our findings suggest that TANGO2 is linked to acyl-CoA metabolism, affecting the acylation of LPA to generate PA, and subsequently impacting the metabolism of fatty acids, generating reactive oxygen species and promoting lipid peroxidation. The enlarged lipid droplets result from the accumulation of peroxidized lipids and a defect in their catabolism. These insights help understand the physiological consequences of TANGO2 mutations and their association with metabolic crises and fatality under starvation and stress conditions.
Article
Genetics & Heredity
Sharayu Jangam, Lauren C. Briere, Kristy L. Jay, Jonathan C. Andrews, Melissa A. Walker, Lance H. Rodan, Frances A. High, Shinya Yamamoto, Michael F. Undiagnosed Diseases Network, David A. Sweetser, Michael F. Wangler
Summary: This study identifies a novel EZH1 variant associated with a neurodevelopmental disorder. Functional analysis in Drosophila suggests that this variant may have a gain-of-function effect.
Article
Genetics & Heredity
Soha Sewani, Mahshid S. Azamian, Bryce A. Mendelsohn, Frederic Tran Mau-Them, Manon Reda, Sophie Nambot, Bertrand Isidor, Jasper J. van der Smagt, Joseph J. Shen, Amelle Shillington, Lori White, Houda Zghal Elloumi, Peter R. Baker II, Shayna Svihovec, Kathleen Brown, Yvonne Koopman-Keemink, Mariette J. V. Hoffer, Inge M. M. Lakeman, Elise Brischoux-Boucher, Maria Kinali, Xiaonan Zhao, Seema R. Lalani, Daryl A. Scott
Summary: The BAZ2B gene is associated with neurodevelopmental phenotypes and structural birth defects. Heterozygous loss-of-function BAZ2B variants can lead to a dominant neurodevelopmental syndrome with incomplete penetrance. The syndrome is characterized by developmental delay, intellectual disability, autism spectrum disorder, speech delay, behavioral abnormalities, seizures, vision-related problems, congenital heart defects, poor fetal growth, and dysmorphic features.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Cardiac & Cardiovascular Systems
Mark Hofmeyer, Garrie J. Haas, Elizabeth Jordan, Jinwen Cao, Evan Kransdorf, Gregory A. Ewald, Alanna A. Morris, Anjali Owens, Brian Lowes, Douglas Stoller, W. H. Wilson Tang, Sonia Garg, Barry H. Trachtenberg, Palak Shah, Salpy V. Pamboukian, Nancy K. Sweitzer, Matthew T. Wheeler, Jane E. Wilcox, Stuart Katz, Stephen Pan, Javier Jimenez, Frank Smart, Jessica Wang, Stephen S. Gottlieb, Daniel P. Judge, Charles K. Moore, Gordon S. Huggins, Daniel D. Kinnamon, Hanyu Ni, Ray E. Hershberger
Summary: Advanced dilated cardiomyopathy (DCM) is associated with a higher probability of pathogenic or likely pathogenic rare variants in DCM genes, which can help assess the risk of outcomes in managing DCM patients and their at-risk family members.
Article
Cardiac & Cardiovascular Systems
Benjamin J. Landis, Lindsey R. Helvaty, Gabrielle C. Geddes, Jiuann-Huey Ivy Lin, Svetlana A. Yatsenko, Cecilia W. Lo, William L. Border, Stephanie Burns Wechsler, Chaya N. Murali, Mahshid S. Azamian, Seema R. Lalani, Robert B. Hinton, Vidu Garg, Kim L. McBride, Jennelle C. Hodge, Stephanie M. Ware
Summary: This study analyzes the association between abnormal chromosomal microarray analysis (CMA) and cardiac phenotypes in patients with congenital heart disease (CHD). The results show that some CHD cases are caused by genomic disorders, some are caused by copy number variants (CNVs), and some are caused by regions of homozygosity. The classification analysis reveals different types of CHD and identifies new CHD types. Different types of CNVs are associated with the complexity of CHD. CNVs containing specific genes are associated with specific phenotypes of CHD. In addition, single-gene CNVs are associated with neuronal-related pathways.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Chemistry, Analytical
Damon T. Leach, Kelly G. Stratton, Jan Irvahn, Rachel Richardson, Bobbie-Jo M. Webb-Robertson, Lisa M. Bramer
Summary: Mass spectrometry is a powerful tool for identifying and analyzing biomolecules in complex biological samples. However, variations between sample batches can lead to systematic errors or biases in the measured abundances. To address this issue, we introduce the malbacR package, which consolidates 11 commonly used batch effect correction methods, allowing users to easily implement and compare different methods.
ANALYTICAL CHEMISTRY
(2023)
Article
Genetics & Heredity
Lot Snijders Blok, Jolijn Verseput, Dmitrijs Rots, Hanka Venselaar, A. Micheil Innes, Connie Stumpel, Katrin Ounap, Karit Reinson, Eleanor G. Seaby, Shane McKee, Barbara Burton, Katherine Kim, Johanna M. van Hagen, Quinten Waisfisz, Pascal Joset, Katharina Steindl, Anita Rauch, Dong Li, Elaine H. Zackai, Sarah E. Sheppard, Beth Keena, Hakon Hakonarson, Andreas Roos, Nicolai Kohlschmidt, Anna Cereda, Maria Iascone, Erika Rebessi, Kristin D. Kernohan, Philippe M. Campeau, Francisca Millan, Jesse A. Taylor, Hanns Lochmuller, Martin R. Higgs, Amalia Goula, Birgitta Bernhard, Danita J. Velasco, Andrew A. Schmanski, Zornitza Stark, Lyndon Gallacher, Lynn Pais, Paul C. Marcogliese, Shinya Yamamoto, Nicholas Raun, Taryn E. Jakub, Jamie M. Kramer, Joery den Hoed, Simon E. Fisher, Han G. Brunner, Tjitske Kleefstra
Summary: We studied WDR5, a broadly studied key protein involved in various biological functions. We found rare de novo germline missense variants in WDR5 that are associated with neurodevelopmental disorders. These variants may disrupt interactions of WDR5 with crucial proteins such as RbBP5 and/or KMT2A/C.
HUMAN GENETICS AND GENOMICS ADVANCES
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Liselot van der Laan, Eline Verberne, Sadegheh Haghshenas, Kathleen Rooney, Michael Levy, Marielle Alders, Saskia M. Maas, Sandra Jansen, Agne Lieden, Britt M. Anderlid, Louise Rafael-Croes, Philippe M. Campeau, Ayeshah Chaudhry, David Koolen, Rolph Pfunt, Anna C. E. Hurst, Frederic Tran Mau-Them, Laetitia Lamber, Ange-Line Bruel, Bertrand Isidor, Marcel Mannens, Bekim Sadikovic, Peter Henneman, Mieke van Haelst
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Kornelia Ellwanger, Eva Bermejo-Sanchez, Evangelista Teresinha, Nicoline Hoogerbrugge, Vincenzo Nigro, Rebecca Schuele, Alain Verloes, Han Brunner, Philippe M. Campeau, Paul Lasko, Birte Zurek, Holm Graessner, Olaf Riess
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Michael Levy, Haley McConkey, Jennifer Kerkhof, Aidin Foroutan, Sadegheh Haghshenas, Jack Reilly, Raissa Relator, Kathleen Rooney, Dimitar Azmanov, Tugce Balci, Siddharth Banka, Jozef Gecz, Peter Henneman, Jennifer Lee, Marcel Mannens, Tony Roscioli, Victoria Siu, David Amor, Gareth Baynam, Nicola Brunetti-Pierri, Eric Bend, Kym Boycott, Philippe M. Campeau, John Christodoulou, David Dyment, Natacha Esber, Jill Fahrner, Mark Fleming, David Genevieve, Barb DuPont, Kristin Kristin D. Kerrnohan, Alisdair McNeill, Leonie Menke, Laurence Faivre, Giuseppe Merla, Paolo Prontera, Cheryl Rockman, Charles Schwartz, Steven Skinner, Roger Stevenson, Antonio Vitobello, Marco Tartaglia, Marielle Alders, Matthew Tedder, Bekim Sadikovic
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)