Article
Oncology
Jeremy M. Grenier, Alexandra J. Borst, Sarah E. Sheppard, Kristen M. Snyder, Dong Li, Lea F. Surrey, Alyaa Al-Ibraheemi, David R. Weber, James R. Treat, Christopher L. Smith, Pablo Laje, Yoav Dori, Denise M. Adams, Michael Acord, Abhay S. Srinivasan
Summary: Complex lymphatic anomalies are challenging to diagnose due to significant overlap among conditions. Genetic analysis has emerged as an additional diagnostic tool, as demonstrated in four cases with PIK3CA variants. The identification of PIK3CA led to targeted treatment with alpelisib, highlighting the genetic overlap among phenotypically diverse lymphatic anomalies.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Biology
Bryn D. Webb, Sara M. Nowinski, Ashley Solmonson, Jaya Ganesh, Richard J. Rodenburg, Joao Leandro, Anthony Evans, Hieu S. Vu, Thomas P. Naidich, Bruce D. Gelb, Ralph J. DeBerardinis, Jared Rutter, Sander M. Houten
Summary: In this study, we reported a patient with pathogenic variants in MCAT, presenting with hypotonia, failure to thrive, nystagmus, and abnormal brain MRI findings. Biallelic variants in MCAT were identified through whole exome sequencing. Protein levels of subunits of complex I and IV, NDUFB8 and COXII respectively, were significantly reduced in lymphoblasts and fibroblasts, as well as SDHB for complex II in fibroblasts. ETC enzyme activities were decreased accordingly. Re-expression of wild-type MCAT rescued the phenotype in patient fibroblasts. This is the first report of a patient with MCAT pathogenic variants and combined oxidative phosphorylation deficiency.
Article
Urology & Nephrology
Veronica Arora, Suliman Khan, Ayman W. El-Hattab, Ratna Dua Puri, Maria Eugenia Rocha, Rijad Merdzanic, Omid Paknia, Christian Beetz, Arndt Rolfs, Aida M. Bertoli-Avella, Peter Bauer, Ishwar C. Verma
Summary: A study identified the causal role of GFRA1 gene variants in bilateral renal agenesis, potentially manifesting as an autosomal recessive, nonsyndromic form. This finding will facilitate early genetic diagnosis and improved genetic counseling for families at risk of BRA.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Genetics & Heredity
Claudio Fiorini, Andrea Degiorgi, Maria Lucia Cascavilla, Concetta Valentina Tropeano, Chiara La Morgia, Marco Battista, Danara Ormanbekova, Flavia Palombo, Michele Carbonelli, Francesco Bandello, Valerio Carelli, Alessandra Maresca, Piero Barboni, Enrico Baruffini, Leonardo Caporali
Summary: We report the first family with a homozygous MECR variant causing an LHON-like optic neuropathy, which pairs the recent MCAT findings, reinforcing the impairment of mtFAS as a novel pathogenic mechanism in LHON.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Guillaume Olivier, Marta Corton, Daniela Intartaglia, Sanne K. Verbakel, Panagiotis Sergouniotis, Guylene Le Meur, Claire-Marie Dhaenens, Helene Naacke, Almudena Avila-Fernandez, Carel B. Hoyng, Jeroen Klevering, Beatrice Bocquet, Agathe Roubertie, Audrey Senechal, Sandro Banfi, Agnes Muller, Christian L. Hamel, Graeme C. Black, Ivan Conte, Susanne Roosing, Xavier Zanlonghi, Carmen Ayuso, Isabelle Meunier, Gael Manes
Summary: This study reveals a previously unreported association between monoallelic or biallelic IMPG1 variants and RP, as well as the identification of new genetic variants associated with this gene. The clinical diagnosis of the IMPG1 retinopathy-associated variant has been revised from benign concentric annular macular dystrophy to RP with early macular involvement.
JOURNAL OF MEDICAL GENETICS
(2021)
Review
Genetics & Heredity
Sandro Michelini, Maurizio Ricci, Roberta Serrani, Shila Barati, Sercan Kenanoglu, Dominika Veselenyiova, Danjela Kurti, Mirko Baglivo, Syed Hussain Basha, Sasi Priya, Astrit Dautaj, Munis Dundar, Juraj Krajcovic, Matteo Bertelli
Summary: Researchers developed a Next-Generation-Sequencing protocol to screen genetic variants related to lymphedema in 246 Italian patients. Seven out of 235 patients were found to carry rare missense variants in the NOTCH1 gene, suggesting its potential role as a novel candidate for genetic predisposition to lymphedema. The study highlights the importance of genetic analysis in understanding the causes of lymphedema.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Review
Genetics & Heredity
Sandro Michelini, Maurizio Ricci, Roberta Serrani, Shila Barati, Sercan Kenanoglu, Dominika Veselenyiova, Danjela Kurti, Mirko Baglivo, Syed Hussain Basha, Sasi Priya, Astrit Dautaj, Munis Dundar, Juraj Krajcovic, Matteo Bertelli
Summary: A Next-Generation-Sequencing protocol was developed to screen genetic variants related to lymphedema, with results suggesting NOTCH1 as a novel candidate gene for lymphedema predisposition.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Kristiana Gordon, Matthew Moore, Malou Van Zanten, Julian Pearce, Maxim Itkin, Brendan Madden, Lakshmi Ratnam, Peter S. Mortimer, Rani Nagaraja, Sahar Mansour
Summary: The RASopathies are a group of genetic conditions caused by mutations in the RAS-MAPK pathway. Central conducting lymphatic abnormalities (CCLA) are a recently described complication associated with these conditions. CCLAs can have severe consequences, such as recurrent chylothoraces, chylopericardium, and chylous ascites, which can lead to significant morbidity and even death. Improved imaging techniques have enhanced our understanding of these complex abnormalities. Treatment is challenging, with diuretics and invasive mechanical drainages being the main approaches.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Thomas Kovesi, Samantha K. Rojas, Kym M. Boycott
Summary: PIEZO1 gene mutations are associated with lymphatic valve formation abnormalities and various lymphatic abnormalities, such as neonatal hydrops, lymphedema, and chylothorax. However, persistent or recurrent chylothorax associated with PIEZO1 gene mutations is rare.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Le Guo, Bob P. H. Engelen, Irene M. G. M. Hemel, Irenaeus F. M. de Coo, Maaike Vreeburg, Suzanne C. E. H. Sallevelt, Debby M. E. Hellebrekers, Ed H. Jacobs, Farah Sadeghi-Niaraki, Florence H. J. van Tienen, Hubert J. M. Smeets, Mike Gerards
Summary: In a Dutch patient with non-consanguineous mitochondrial encephalomyopathy, two compound heterozygous variants in SLIRP were found through whole exome sequencing. Experimental results showed that the SLIRP variants led to reduced mitochondrial mass and impaired OXPHOS activity in patient fibroblasts. Restoration of wild-type SLIRP expression partly recovered OXPHOS activity, confirming the causality of the variants.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Cell Biology
Yanwei Sha, Wensheng Liu, Lin Li, Mario Serafimovski, Vladimir Isachenko, Youzhu Li, Jing Chen, Bangrong Zhao, Yifeng Wang, Xiaoli Wei
Summary: This study identified pathogenic variants in the X-linked gene ACTRT1 in patients with acephalic spermatozoa syndrome, suggesting that mutations in this gene may contribute to the syndrome. Knockout mice of Actrt1 showed a similar phenotype, supporting this hypothesis. The findings provide valuable insights for clinicians and researchers on the genetic etiology and therapeutic strategies for patients with acephalic spermatozoa syndrome.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Svetlana A. Yatsenko, Fatih Gurbuz, Ali Kemal Topaloglu, Andrea J. Berman, Pierre-Marie Martin, Marta Rodrigue-Escriba, Yingying Qin, Aleksandar Rajkovic
Summary: This study identified pathogenic variants in the ZSWIM7 gene associated with primary ovarian insufficiency (POI), highlighting the importance of this gene in DNA damage response during meiosis and its role in ovarian development and function. Characterization of patients with defects in DNA repair genes has important diagnostic and prognostic consequences for clinical management and reproductive decisions.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Genetics & Heredity
Margot A. Cousin, Blake A. Creighton, Keith A. Breau, Rebecca C. Spillmann, Erin Torti, Sruthi Dontu, Swarnendu Tripathi, Deepa Ajit, Reginald J. Edwards, Simone Afriyie, Julia C. Bay, Kathryn M. Harper, Alvaro A. Beltran, Lorena J. Munoz, Liset Falcon Rodriguez, Michael C. Stankewich, Richard E. Person, Yue Si, Elizabeth A. Normand, Amy Blevins, Alison S. May, Louise Bier, Vimla Aggarwal, Grazia M. S. Mancini, Marjon A. van Slegtenhorst, Kirsten Cremer, Jessica Becker, Hartmut Engels, Stefan Aretz, Jennifer J. MacKenzie, Eva Brilstra, Koen L. I. van Gassen, Richard H. van Jaarsveld, Renske Oegema, Gretchen M. Parsons, Paul Mark, Ingo Helbig, Sarah E. McKeown, Robert Stratton, Benjamin Cogne, Bertrand Isidor, Pilar Cacheiro, Damian Smedley, Helen V. Firth, Tatjana Bierhals, Katja Kloth, Deike Weiss, Cecilia Fairley, Joseph T. Shieh, Amy Kritzer, Parul Jayakar, Evangeline Kurtz-Nelson, Raphael A. Bernier, Tianyun Wang, Evan E. Eichler, Ingrid M. B. H. van de Laar, Allyn McConkie-Rosell, Marie T. McDonald, Jennifer Kemppainen, Brendan C. Lanpher, Laura E. Schultz-Rogers, Lauren B. Gunderson, Pavel N. Pichurin, Grace Yoon, Michael Zech, Robert Jech, Juliane Winkelmann, Adriana S. Beltran, Michael T. Zimmermann, Brenda Temple, Sheryl S. Moy, Eric W. Klee, Queenie K. -G. Tan, Damaris N. Lorenzo
Summary: SPTBN1 mutations cause a neurodevelopmental syndrome with intellectual disability, language and motor delays, and other features. Heterozygous SPTBN1 variants disrupt beta II-spectrin stability, binding to molecular partners, and disturb cytoskeleton organization and dynamics, suggesting compromise of neural development and function. This study expands the understanding of spectrinopathies affecting the brain and highlights the critical role of beta II-spectrin in the central nervous system.
Article
Cell Biology
Deepa S. Rajan, Sukhleen Kour, Tyler R. Fortuna, Margot A. Cousin, Sarah S. Barnett, Zhiyv Niu, Dusica Babovic-Vuksanovic, Eric W. Klee, Brian Kirmse, Micheil Innes, Siri Lynne Rydning, Kaja K. Selmer, Magnus Dehli Vigeland, Anne Kjersti Erichsen, Andrea H. Nemeth, Francisca Millan, Catherine DeVile, Katherine Fawcett, Adrien Legendre, David Sims, Ricardo Parolin Schnekenberg, Lydie Burglen, Sandra Mercier, Somayeh Bakhtiari, Encarnacion Martinez-Salas, Kristen Wigby, Jerica Lenberg, Jennifer R. Friedman, Michael C. Kruer, Udai Bhan Pandey
Summary: This study discovered biallelic variants in the GEMIN5 gene among nine affected individuals, leading to abnormal protein structure and reduced expression of snRNP complex proteins. The research expands on the phenotypic spectrum associated with GEMIN5-related disease, providing insights into patients with spastic ataxia, cerebellar atrophy, and motor predominant developmental delay.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Vassos Neocleous, Pavlos Fanis, Meropi Toumba, Barbara Gorka, Ioanna Kousiappa, George A. Tanteles, Michalis Iasonides, Nicolas C. Nicolaides, Yiolanda P. Christou, Kyriaki Michailidou, Stella Nicolaou, Savvas S. Papacostas, Athanasios Christoforidis, Andreas Kyriakou, Dimitrios Vlachakis, Nicos Skordis, Leonidas A. Phylactou
Summary: The study identified three pathogenic MKRN3 variants and indicated a founder effect phenomenon for the most prevalent variant p.Gly312Asp exclusively found in the Cypriot CPP cohort. Additionally, rare likely pathogenic variants were found in other genes.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Pathology
Saumya E. Samaraweera, Tatjana Geukens, Debora A. Casolari, Tran Nguyen, Caitlyn Sun, Sheree Bailey, Sarah Moore, Jinghua Feng, Andreas W. Schreiber, Wend T. Parker, Anna L. Brown, Carolyn Butcher, Peter G. Bardy, Michael Osborn, Hamish S. Scott, Dipti Talaulikar, Carolyn S. Grove, Christopher N. Hahn, Richard J. D'andrea, David M. Ross
Summary: The identification of a somatic mutation associated with myeloid malignancy is crucial in the diagnosis of myelo-proliferative neoplasms (MPNs). Individuals who test negative for common mutations in JAK2, CALR, and MPL, referred to as 'triple-negative', present a diagnostic challenge. In this study, an extended sequencing panel was used to analyze 44 triple-negative MPN patients, revealing low-frequency mutations in JAK2, MPL, and CALR in some patients, as well as less common mutations in the JAK-STAT signaling pathway and other recurrently mutated genes. Analysis of rare MPL variants in one patient with thrombocytosis demonstrated the importance of functional assays in determining pathogenicity.
Article
Hematology
Jamie E. Flerlage, Jason R. Myers, Jamie L. Maciaszek, Ninad Oak, Sara R. Rashkin, Yawei Hui, Yong-Dong Wang, Wenan Chen, Gang Wu, Ti-Cheng Chang, Kayla Hamilton, Saima S. Tithi, Lynn R. Goldin, Melissa Rotunno, Neil Caporaso, Aurelie Vogt, Deborah Flamish, Kathleen Wyatt, Jia Liu, Margaret Tucker, Christopher N. Hahn, Anna L. Brown, Hamish S. Scott, Charles Mullighan, Kim E. Nichols, Monika L. Metzger, Mary L. McMaster, Jun J. Yang, Evadnie Rampersaud
Summary: Familial aggregation of HL has been shown to have a genetic component. In this study, whole genome sequencing was performed on individuals with and without HL from pedigrees with multiple affected relatives. A total of 44 HL-risk variants were identified, including both coding and noncoding variants. The study also identified several novel variants and observed segregation patterns in most pedigrees.
Article
Hematology
Caner Saygin, Gregory Roloff, Christopher N. Hahn, Rakchha Chhetri, Saar Gill, Hany Elmariah, Chetasi Talati, Emma Nunley, Guimin Gao, Aelin Kim, Michael Bishop, Satyajit Kosuri, Soma Das, Deepak Singhal, Parvathy Venugopal, Claire C. Homan, Anna Brown, Hamish S. Scott, Devendra Hiwase, Lucy A. Godley
Summary: There is growing recognition that pathogenic germ line variants play a role in the development of hematopoietic cancers. Patients with myeloid malignancies and deleterious germ line DDX41 variants have a higher incidence of severe acute GVHD. The use of posttransplant cyclophosphamide can reduce the risk of severe acute GVHD in these patients.
Review
Hematology
Claire C. Homan, Hamish S. Scott, Anna L. Brown
Summary: Hereditary platelet disorders (HPDs) are a diverse group of blood disorders with variable clinical impact. Genetic causes for these disorders are numerous, and multigene panels are being used to uncover missing heritability more efficiently. Some of these disorders also increase the risk of developing hematological malignancy (HM), and each disorder has distinct penetrance of HM and associated somatic alterations. Integrating these advances into routine clinical practice and optimizing management and surveillance of patients and carriers are the current challenges.
Letter
Hematology
Devendra Hiwase, Christopher Hahn, Elizabeth Ngoc Hoa Tran, Rakchha Chhetri, Anmol Baranwal, Aref Al-Kali, Kirsty Sharplin, Dariusz Ladon, Rachel Hollins, Patricia Greipp, Monika Kutyna, Hassan Alkhateeb, Talha Badar, Paul Wang, David M. Ross, Deepak Singhal, Naranie Shanmuganathan, Peter Bardy, Ashanka Beligaswatte, David Yeung, Mark R. Litzow, Abhishek Mangaonkar, Pratyush Giri, Cindy Lee, Angie Yong, Noemi Horvath, Nimit Singhal, Raghu Gowda, William Hogan, Naseema Gangat, Mrinal Patnaik, Kebede Begna, Ing S. Tiong, Andrew Wei, Sharad Kumar, Anna Brown, Hamish Scott, Daniel Thomas, Chung H. Kok, Ayalew Tefferi, Mithun Vinod Shah
Correction
Genetics & Heredity
Pleuntje J. van der Sluijs, Marieke Joosten, Caroline Alby, Tania Attie-Bitach, Kelly Gilmore, Christele Dubourg, Melanie Fradin, Tianyun Wang, Evangeline C. Kurtz-Nelson, Kaitlyn P. Ahlers, Peer Arts, Christopher P. Barnett, Myla Ashfaq, Anwar Baban, Myrthe van den Born, Sarah Borrie, Tiffany Busa, Alicia Byrne, Miriam Carriero, Claudia Cesario, Karen Chong, Anna Maria Cueto-Gonzalez, Jennifer C. Dempsey, Karin E. M. Diderich, Dan Doherty, Stense Farholt, Erica H. Gerkes, Svetlana Gorokhova, Lutgarde C. P. Govaerts, Pernille A. Gregersen, Scott E. Hickey, Mathilde Lefebvre, Francesca Mari, Jelena Martinovic, Hope Northrup, Melanie O'Leary, Kareesma Parbhoo, Sophie Patrier, Bernt Popp, Fernando Santos-Simarro, Corinna Stoltenburg, Christel Thauvin-Robinet, Elisabeth Thompson, Anneke T. Vulto-van Silfhout, Farah R. Zahir, Hamish S. Scott, Rachel K. Earl, Evan E. Eichler, Neeta L. Vora, Yael Wilnai, Jessica L. Giordano, Ronald J. Wapner, Jill A. Rosenfeld, Monique C. Haak, Gijs W. E. Santen
GENETICS IN MEDICINE
(2023)
Article
Multidisciplinary Sciences
Jan Kazenwadel, Parvathy Venugopal, Anna Oszmiana, John Toubia, Luis Arriola-Martinez, Virginia Panara, Sandra G. Piltz, Chris Brown, Wanshu Ma, Andreas W. Schreiber, Katarzyna Koltowska, Samir Taoudi, Paul Q. Thomas, Hamish S. Scott, Natasha L. Harvey
Summary: In this study, a novel enhancer element responsible for regulating Prox1 expression in lymphatic endothelial cells was identified. Genome editing of this enhancer resulted in perinatal death and profound lymphatic vascular defects in mutant mice. The mutant mice also exhibited altered gene expression profiles and acquired the ability to generate hematopoietic cells. These findings demonstrate the importance of this enhancer in controlling lymphatic endothelial cell identity and reveal the previously unknown hemogenic capacity of the lymphatic endothelium.
Article
Biochemistry & Molecular Biology
Alicia B. Byrne, Peer Arts, Thuong T. Ha, Karin S. Kassahn, Lynn S. Pais, Anne O'Donnell-Luria, Milena Babic, Mahalia S. B. Frank, Jinghua Feng, Paul Wang, David M. Lawrence, Leila Eshraghi, Luis Arriola, John Toubia, Hung Nguyen, George McGillivray, Jason Pinner, Fiona McKenzie, Rebecca Morrow, Jill Lipsett, Nick Manton, T. Yee Khong, Lynette Moore, Jan E. Liebelt, Andreas W. Schreiber, Sarah L. King-Smith, Tristan S. E. Hardy, Matilda R. Jackson, Christopher P. Barnett, Hamish S. Scott, Francois Aguet, Harindra M. Arachchi, Christina A. Austin-Tse, Larry Babb, Samantha M. Baxter, Harrison Brand, Alicia B. Byrne, Jaime Chang, Katherine R. Chao, Ryan L. Collins, Beryl Cummings, Kayla Delano, Stephanie P. DiTroia, Eleina England, Emily Evangelista, Selin Everett, Laurent C. Francioli, Jack Fu, Vijay S. Ganesh, Kiran Garimella, Laura D. Gauthier, Julia K. Goodrich, Sanna Gudmundsson, Stacey J. Hall, Yongqing Huang, Steve Jahl, Kristen M. Laricchia, Kathryn E. Larkin, Monkol Lek, Gabrielle Lemire, Rachel B. Lipson, Alysia Kern Lovgren, Daniel G. MacArthur, Brian E. Mangilog, Stacy Mano, Jamie L. Marshall, Thomas E. Mullen, Kevin K. Nguyen, Emily O'Heir, Melanie C. O'Leary, Ikeoluwa A. Osei-Owusu, Lynn S. Pais, Jorge Perez de Acha Chavez, Emma Pierce-Hoffman, Heidi L. Rehm, Milan Serrano, Moriel Singer-Berk, Hana Snow, Matthew Solomonson, Rachel G. Son, Abigail Sveden, Michael Talkowski, Grace Tiao, Miriam S. Udler, Zaheer Valivullah, Elise Valkanas, Grace E. VanNoy, Qingbo S. Wang, Nicholas A. Watts, Ben Weisburd, Clara E. Williamson, Michael W. Wilson, Lauren Witzgall, Monica H. Wojcik, Isaac Wong, Jordan C. Wood, Shifa Zhang, Disna Abeysuriya, Lesley C. Ades, David J. Amor, Susan Arbuckle, Madhura Bakshi, Christopher P. Barnete, Bligh Berry, Tiffany Boughtwood, Adam Bournazos, Alessandra Bray, Fiona Chan, Yuen Chan, Clara Chung, Jonathan Clark, Jackie Collett, Alison Colley, Felicity Collins, Sandra Cooper, Mark A. Corbett, Jane E. Dahlstrom, Peter Dargaville, Janene Davies, Tenielle Davis, Jarrad Dearman, Jayanthi Dissanayake, Julia Dobbins, Helen Doyle, Andrew Dubowsky, Matt Edwards, Lisa J. Ewans, Mitali Fadia, Andrew Fennell, Ken Finlay, Andrew French, Kathryn Friend, Alison E. Gardner, Jozef Gecz, Nicole Graf, Eric A. Haan, Georgina Hollingsworth, Ari E. Horton, Denise Howting, Matthew F. Hunter, Gareth Jevon, Benjamin Kamien, Debra Kennedy, T. Yee Khong, Michael Krivanek, Thessa Kroes, Emma Krzesinski, Edward Kwan, Stephanie Lau, Shannon LeBlanc, Jan Liebelt, Suzanna Lindsey-Temple, Jill Lipsett, Christine K. C. Loo, Julia Low, Amali Mallawaarachchi, Nick Manton, Admire Matsika, Tessa Mattiske, Julie McGaughran, George McGillivray, Lesley McGregor, Fiona McKenzie, Namita Mittal, Ali Moghimi, Lynette Moore, Hatice Mutlu Albayrak, Jessica Ng, Jillian Nicholl, Nicholas Pachter, John Papadimitriou, Renae Parker, Sarah Parsons, Chirag Patel, Rhonda Pawlowski, Luis A. Perez-Jurado, Jason R. Pinner, Katerina Politis, Cathryn Poulton, Theresa Power, Michael Quinn, Sulekha Rajagopalan, Matthew Regan, Jonathan Rodgers, Steuart Rorke, Rani Sachdev, Suzanne Sallevelt, Sarah A. Sandaradura, Maryam Shamassi, Roshan Shamon, Isabella Sherburn, Ennie Slee, Annalisa Solinas, Ella Sugo, Elizabeth Thompson, Sagarika Tripathy, Anand Vasudevan, Melisa Vazquez, Kunal Verma, Mthulisi Viki, Mathew Wallis, Dani L. Webber, Martin Weber, Karen Whale, Meredith Wilson, Lisa Worgan, Sui Yu
Summary: We evaluated 'genomic autopsy' as an adjunct to standard autopsy for families who experienced fetal or newborn death. The study provided genetic diagnoses for 105 families, revealing severe atypical in utero presentations of known genetic disorders and identifying novel phenotypes and disease genes. Our findings emphasize the clinical importance of genomic investigations in pregnancy loss and perinatal death, highlighting the potential for accurate counseling in future pregnancies.
Article
Genetics & Heredity
Zornitza Stark, Tiffany Boughtwood, Matilda Haas, Jeffrey Braithwaite, Clara L. Gaff, Ilias Goranitis, Amanda B. Spurdle, David P. Hansen, Oliver Hofmann, Nigel Laing, Sylvia Metcalfe, Ainsley J. Newson, Hamish S. Scott, Natalie Thorne, Robyn L. Ward, Marcel E. Dinger, Stephanie Best, Janet C. Long, Sean M. Grimmond, John Pearson, Nicola Waddell, Christopher P. Barnett, Matthew Cook, Michael Field, David Fielding, Stephen B. Fox, Jozef Gecz, Adam Jaffe, Richard J. Leventer, Paul J. Lockhart, Sebastian Lunke, Andrew J. Mallett, Julie McGaughran, Linda Mileshkin, Katia Nones, Tony Roscioli, Ingrid E. Scheffer, Christopher Semsarian, Cas Simons, David M. Thomas, David R. Thorburn, Richard Tothill, Deborah White, Sally Dunwoodie, Peter T. Simpson, Peta Phillips, Marie-Jo Brion, Keri Finlay, Michael CJ. Quinn, Tessa Mattiske, Emma Tudini, Kirsten Boggs, Sean Murray, Kathy Wells, John Cannings, Andrew H. Sinclair, John Christodoulou, Kathryn N. North
Summary: Australian Genomics is a national collaborative partnership that aims to integrate genomics into healthcare through a whole-of-system approach. It has evaluated genomic testing outcomes in over 5,200 individuals across rare disease and cancer studies and provided evidence-based changes in policy and practice, resulting in government funding and access to genomic tests. It has also developed national skills, infrastructure, policy, and data resources to support data sharing and improve clinical genomic delivery.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Hematology
Naranie Shanmuganathan, Carol Wadham, NurHezrin Shahrin, Jinghua Feng, Daniel Thomson, Paul Wang, Verity Saunders, Chung Hoow Kok, Rob M. King, Rosalie R. Kenyon, Ming Lin, Ilaria S. Pagani, David M. Ross, Agnes S. M. Yong, Andrew P. Grigg, Anthony K. Mills, Anthony P. Schwarer, Jodi Braley, Haley Altamura, David T. Yeung, Hamish S. Scott, Andreas W. Schreiber, Timothy P. Hughes, Susan Branford
Summary: The presence of additional genetic abnormalities in chronic myeloid leukemia patients at diagnosis is associated with treatment failure and poorer response rates, despite proactive treatment intervention strategies. Incorporating genomic risk assessment into the treatment of CML is necessary.
Article
Endocrinology & Metabolism
Dominyka Batkovskyte, Fiona McKenzie, Fulya Taylan, Pelin Ozlem Simsek-Kiper, Sarah M. Nikkel, Hirofumi Ohashi, Roger E. Stevenson, Thuong Ha, Denise P. Cavalcanti, Hiroyuki Miyahara, Steven A. Skinner, Miguel A. Aguirre, Zuehal Akcoeren, Gulen Eda Utine, Tillie Chiu, Kenji Shimizu, Anna Hammarsjoe, Koray Boduroglu, Hannah W. Moore, Raymond J. Louie, Peer Arts, Allie N. Merrihew, Milena Babic, Matilda R. Jackson, Nikos Papadogiannakis, Anna Lindstrand, Ann Nordgren, Christopher P. Barnett, Hamish S. Scott, Andrei S. Chagin, Gen Nishimura, Giedre Grigelioniene
Summary: Lethal short-limb skeletal dysplasia Al-Gazali type is a rare disorder with unknown genetic etiology. A study involving nine patients with clinical features consistent with this disorder identified disease-causing variants in ADAMTSL2, shedding light on the genetic cause and highlighting the importance of analyzing the pseudogene region. This study enhances our understanding of Al-Gazali skeletal dysplasia and its association with ADAMTSL2-related disorders.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Sebastian Lunke, Sophie. E. E. Bouffler, Chirag. V. V. Patel, Sarah. A. A. Sandaradura, Meredith Wilson, Jason Pinner, Matthew. F. F. Hunter, Christopher. P. P. Barnett, Mathew Wallis, Benjamin Kamien, Tiong. Y. Y. Tan, Mary-Louise Freckmann, Belinda Chong, Dean Phelan, David Francis, Karin. S. S. Kassahn, Thuong Ha, Song Gao, Peer Arts, Matilda. R. S. R. Jackson, Hamish. S. S. Scott, Stefanie Eggers, Simone Rowley, Kirsten Boggs, Ana Rakonjac, Gemma. R. R. Brett, Michelle. G. G. de Silva, Amanda Springer, Michelle Ward, Kirsty Stallard, Cas Simons, Thomas Conway, Andreas Halman, Nicole. J. J. Van Bergen, Tim Sikora, Liana. N. N. Semcesen, David. A. A. Stroud, Alison. G. G. Compton, David. R. R. Thorburn, Katrina. M. M. Bell, Simon Sadedin, Kathryn. N. N. North, John Christodoulou, Zornitza Stark
Summary: A report from the Australian Acute Care Genomics programme demonstrates the clinical utility of integrating rapid whole-genome sequencing and multi-omic analyses in diagnosing and treating critically ill infants and children with rare diseases. Over a span of 2 years, the program provided whole-genome sequencing to 290 families and achieved a diagnostic yield of 54%. The results highlight the potential of incorporating multi-omic approaches into mainstream diagnostic practice for rare disease genomic testing.
Review
Oncology
Jiarna R. Zerella, Claire C. Homan, Peer Arts, Anna L. Brown, Hamish S. Scott, Christopher N. Hahn
Summary: Transcription factors (TFs) play a critical role in the development of tissues and control the behavior of hematopoietic stem and progenitor cells. Understanding the networks and dynamics of hematopoietic transcription factors is essential for understanding normal hematopoiesis and disease progression. This review focuses on TFs predisposing to bone marrow failure and hematological malignancy, and explores potential biological mechanisms and candidate TF genes. A better understanding of hematopoietic TFs will aid in the development of preventative strategies and targeted treatments.
FRONTIERS IN ONCOLOGY
(2023)
Correction
Biochemistry & Molecular Biology
Alicia B. Byrne, Peer Arts, Thuong T. Ha, Karin S. Kassahn, Lynn S. Paris, Anne O'Donnell-Luria, Milena Babic, Mahalia S. B. Frank, Jinghua Feng, Paul Wang, David M. Lawrence, Leila Eshraghi, Luis Arriola, John Toubia, Hung Nguyen, George McGillivray, Jason Pinner, Fiona McKenzie, Rebecca Morrow, Jill Lipsett, Nick Manton, T. Yee Khong, Lynette Moore, Jan E. Liebelt, Andreas W. Schreiber, Sarah L. King-Smith, Tristan S. E. Hardy, Matilda R. Jackson, Christopher P. Barnett, Hamish S. Scott, Broad Inst Ctr Mendelian Genomics, Genomic Autopsy Study Res Network