Article
Genetics & Heredity
Alexis V. V. Rioux, Nicolas A. D. Bergeron, Julie Riopel, Nicolas Marcoux, Catherine Theriault, Peter V. V. Gould, Alexandre P. P. Garneau, Paul Isenring
Summary: RMND1 was identified as a gene associated with mitochondriopathy less than 12 years ago. The most common phenotype related to this gene is an early onset, severe form of encephalomyopathy. However, milder and later onset presentations have been reported. We describe a case of a 61-year-old white female with RMND1 insufficiency who showed various manifestations, including ovarian insufficiency, sensorineural hearing loss, chronic renal failure, and others. This case is of great translational interest as it suggests the possibility of near-normal life expectancies, highlights the wide clinical spectrum of RMND1-associated conditions, and raises questions about the use of eponyms and syndromic features in diagnosing multisystemic phenotypes.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Biochemistry & Molecular Biology
Pratyusha Bala, Anurag Kumar Singh, Padmavathi Kavadipula, Viswakalyan Kotapalli, Radhakrishnan Sabarinathan, Murali Dharan Bashyam
Summary: Early-onset sporadic rectal cancer is a unique and predominant subtype of colorectal cancer in India, with ARID2 identified as a novel tumor suppressor that significantly influences tumorigenic features and tumor formation in CRC.
Article
Clinical Neurology
Ekaterina Kazakova, Jose Alberto Tellez-Martinez, Leonardo Flores-Lagunes, Ana Luisa Sosa-Ortiz, Karol Carillo-Sanchez, Carolina Molina-Garay, Carlos Alberto Gonzalez-Dominguez, Marco Jimenez-Olivares, Francisca Fernandez-Valverde, Edwin Steven Vargas-Canas, Martha Elisa Vazquez-Memije, Ethel Awilda Garcia-Latorre, Ivan Martinez-Duncker, Carmen Alaez-Verson
Summary: This study reports the first Mexican case of AARS2 mutations causing primary ovarian failure, uterus infantilis, and early-onset dementia secondary to leukoencephalopathy. Detailed clinical, clinimetric, neuroimaging, and molecular studies were conducted. The study expands the genetic and phenotypic spectrum of AARS2-related dementia with leukoencephalopathy and ovarian failure and characterizes novel molecular variants.
FRONTIERS IN NEUROLOGY
(2023)
Article
Allergy
Miriam Gross, Carsten Speckmann, Annette May, Tania Gajardo-Carrasco, Katharina Wustrau, Sarah Lena Maier, Marcus Panning, Daniela Huzly, Abbas Agaimy, Yenan T. Bryceson, Sharon Choo, C. W. Chow, Gregor Dueckers, Anders Fasth, Sylvie Fraitag, Katja Graewe, Sabine Haxelmans, Dirk Holzinger, Ole Hudowenz, Judith M. Huebschen, Claudia Khurana, Korbinian Kienle, Roman Klifa, Klaus Korn, Heinz Kutzner, Tim Laemmermann, Svea Ledig, Dan Lipsker, Marie Meeths, Nora Naumann-Bartsch, Jelena Rascon, Anne Schaenzer, Maximilian Seidl, Bianca Tesi, Christelle Vauloup-Fellous, Beate Vollmer-Kary, Klaus Warnatz, Claudia Wehr, Benedicte Neven, Pablo Vargas, Fernando E. Sepulveda, Kai Lehmberg, Annette Schmitt-Graeff, Stephan Ehl
Summary: This study investigated the defective effector mechanism allowing rubella vaccine virus persistence in granulomas by studying patients with cytotoxicity defects and granuloma. The results suggest a critical role of T cells in rubella elimination.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Hematology
Radha Ramanan, James D. McFadyen, Andrew C. Perkins, Huyen A. Tran
Summary: Congenital fibrinogen disorders (CFDs) are a group of heterogeneous diseases with diverse clinical manifestations and molecular lesions. The correlation between phenotype and genotype is still poorly understood. This review explores the current understanding of the genetic landscape of CFDs and discusses the potential influence of oligogenic inheritance on phenotypic heterogeneity, as well as the benefits and challenges of sequencing technology in uncovering new findings. Further research is needed to achieve precise diagnosis, prognosis, and targeted management for this complex group of patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Gerard Temprano-Sagrera, Colleen M. Sitlani, William P. Bone, Miguel Martin-Bornez, Benjamin F. Voight, Alanna C. Morrison, Scott M. Damrauer, Paul S. de Vries, Nicholas L. Smith, Maria Sabater-Lleal
Summary: This study discovered four novel genetic loci by combining summary data of different hemostatic traits and disease events, contributing to the understanding of the relationship between hemostasis and cardiovascular events and elucidating common genetic factors between these traits.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Biochemistry & Molecular Biology
Santiago Milla-Navarro, Mateo Pazo-Gonzalez, Francisco Germain, Pedro de la Villa
Summary: Recent technological development requires new approaches to address the problem of blindness. A new mouse model has successfully eliminated photosensitive cells in the retina, providing a potential tool for studying ophthalmological treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Jessica A. Plante, Kenneth S. Plante, Vsevolod L. Popov, Divya P. Shinde, Steven G. Widen, Michaela Buenemann, Mauricio L. Nogueira, Nikos Vasilakis
Summary: Ilheus virus (ILHV) is a mosquito-borne flavivirus found in Central and South America and the Caribbean. It can be detected in various mosquito genera and is primarily transmitted by birds. The genetic and morphological characterization of ten ILHV strains revealed conservation in the untranslated regions but divergence within the open reading frame, indicating a typical flavivirus structure and organization. This research lays the groundwork for further studies on ILHV's transmission cycles, pathogenicity, and potential emergence.
Review
Allergy
Matthew S. Krantz, V. Eric Kerchberger, Wei-Qi Wei
Summary: The field of immunogenomics has the potential to accelerate genetic discovery through the use of electronic health records (EHRs) linked to DNA biobanks. Novel analysis methods in deep phenotyping of EHR data allow researchers to uncover genetic risk factors for immune-mediated diseases and adverse drug reactions.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2022)
Article
Endocrinology & Metabolism
Zhenyu Li, Qingming Jiang, Xinyu Chen, Yu Xiao, Jue Xiao
Summary: This study reported a rare case of primary hepatoid adenocarcinoma of the gallbladder with MB21D2, GALNT12, and ARID2 mutations, providing a theoretical basis for studying genetic changes in rare tumors.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Clinical Neurology
Arthur Stefanski, Eduardo Perez-Palma, Tobias Bruenger, Ludovica Montanucci, Cornelius Gati, Chiara Kloeckner, Katrine M. Johannesen, Kimberly Goodspeed, Marie Macnee, Alexander T. Deng, Angel Aledo-Serrano, Artem Borovikov, Maina Kava, Arjan M. Bouman, M. J. Hajianpour, Deb K. Pal, Marc Engelen, Eveline E. O. Hagebeuk, Marwan Shinawi, Alexis R. Heidlebaugh, Kathryn Oetjens, Trevor L. Hoffman, Pasquale Striano, Amanda S. Freed, Line Futtrup, Thomas Balslev, Anna Abuli, Leslie Danvoye, Damien Lederer, Tugce Balci, Maryam Nabavi Nouri, Elizabeth Butler, Sarah Drewes, Kalene van Engelen, Katherine B. Howell, Jean Khoury, Patrick May, Marena Trinidad, Steven Froelich, Johannes R. Lemke, Jacob Tiller, Amber N. Freed, Jing-Qiong Kang, Arthur Wuster, Rikke S. Moller, Dennis Lal
Summary: Genetic variants in the SLC6A1 gene can cause a broad spectrum of phenotypic diseases by altering the protein function. Through the aggregation of genetic and clinical data, as well as functional data, the study found potential associations between variant positions on the GAT1 3D structure, variant pathogenicity, altered molecular function, and phenotype severity.
Article
Oncology
Miaomiao Shen, Xiaona Yin, Yanfeng Bai, Huizhi Zhang, Guoqing Ru, Xianglei He, Xiaodong Teng, Guorong Chen, Ming Zhao
Summary: Papillary renal neoplasm with reverse polarity (PRNRP) is a rare renal tumor that is clinically, morphologically, and molecularly different from papillary renal cell carcinoma (RCC). This study aimed to investigate the clinicopathological and molecular genetic features of PRNRP. The study identified 16 cases of PRNRP and found unique morphological and immunohistochemical features, as well as recurrent KRAS mutation in PRNRP.
FRONTIERS IN ONCOLOGY
(2022)
Article
Clinical Neurology
Maria Rosario Almeida, Ana Rita Silva, Ines Elias, Carolina Fernandes, Rita Machado, Orlando Galego, Gustavo Cordeiro Santo
Summary: CADASIL, caused by NOTCH3 mutations, shows phenotypic variability even with the same pathogenic variant. Two siblings with aggressive clinical phenotype carried NOTCH3 and SQSTM1 pathogenic variants, potentially exacerbating disease progression. Contribution of SQSTM1 to clinical heterogeneity in CADASIL patients, particularly those with early cognitive impairment, is highlighted, suggesting the need for expanded genetic analysis.
JOURNAL OF NEUROLOGY
(2021)
Article
Microbiology
Carolina Lopes, Sergio Santos-Silva, Carolina Nunes, Susana Mendes, Catarina Costa, Erica Brazio, Teresa Coutinho, Filipa Teixeira Rodrigues, Joao R. Mesquita, Ana Claudia Coelho, Luis Cardoso, Ana Patricia Lopes
Summary: This study is the first report of the genetic sequencing of Synhimantus laticeps in a long-eared owl (A. otus) from Portugal. The presence of nematodes in the oral cavity of the owl was confirmed through morphological and genetic analysis.
Article
Urology & Nephrology
Jenny Patterson, Zoe Jacob, Ben C. Reynolds
Summary: Monogenic causes of paediatric nephrocalcinosis can present with extensive phenotypic variability. In this case, a 14-year-old male with incidentally identified nephrocalcinosis alongside growth impairment and dental anomalies was confirmed to have Bartter syndrome type II through genetic investigation. The presence of amelogenesis imperfecta is rare in inherited tubulopathies, making this case exceptional in its presentation. The utility of a phenotype-driven genetic panel in resolving atypical presentations of nephrocalcinosis is highlighted, allowing for precise diagnosis, tailored therapy, and prognostication.
CLINICAL KIDNEY JOURNAL
(2022)
Article
Hematology
Courtney D. DiNardo, Sangeetha Venugopal, Curtis Lachowiez, Koichi Takahashi, Sanam Loghavi, Guillermo Montalban-Bravo, Xuemei Wang, Hetty Carraway, Mikkael Sekeres, Ameenah Sukkur, Danielle Hammond, Kelly Chien, Abhishek Maiti, Lucia Masarova, Koji Sasaki, Yesid Alvarado, Tapan Kadia, Nicholas J. Short, Naval Daver, Gautam Borthakur, Farhad Ravandi, Hagop M. Kantarjian, Bhumika Patel, Amy Dezern, Gail Roboz, Guillermo Garcia-Manero
Summary: The combination of enasidenib with azacitidine showed a 74% overall response rate in newly diagnosed mIDH2 MDS patients, while enasidenib monotherapy achieved a 35% response rate in patients after HMA failure. These findings demonstrate that enasidenib is an effective treatment option for mIDH2 MDS.
Article
Hematology
Hideki Makishima, Ryunosuke Saiki, Yasuhito Nannya, Sophia Korotev, Carmelo Gurnari, June Takeda, Yukihide Momozawa, Steve Best, Pramila Krishnamurthy, Tetsuichi Yoshizato, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Yasunobu Nagata, Nobuyuki Kakiuchi, Makoto Onizuka, Kenichi Chiba, Hiroko Tanaka, Ayana Kon, Yotaro Ochi, Masahiro M. Nakagawa, Rurika Okuda, Takuto Mori, Akinori Yoda, Hidehiro Itonaga, Yasushi Miyazaki, Masashi Sanada, Takayuki Ishikawa, Shigeru Chiba, Hisashi Tsurumi, Senji Kasahara, Carsten Mueller-Tidow, Akifumi Takaori-Kondo, Kazuma Ohyashiki, Toru Kiguchi, Fumihiko Matsuda, Joop H. Jansen, Chantana Polprasert, Piers Blombery, Yoichiro Kamatani, Sator Miyano, Luca Malcovati, Torsten Haferlach, Michiaki Kubo, Mario Cazzola, Austin G. Kulasekararaj, Lucy A. Godley, Jaroslaw P. Maclejewski, Seishi Ogawa
Summary: DDX41 gene mutations play an important role in late-onset myeloid neoplasms, but many crucial features of DDX41-mutated neoplasms still need to be elucidated. This study comprehensively characterized DDX41-mutated neoplasms and found that DDX41 risk variants accounted for 80% of known genetic predispositions to myeloid neoplasms in adults. Additionally, DDX41 risk alleles were significantly enriched in Japanese cases and more prominent in males compared to females.
Letter
Hematology
Tariq Kewan, Waled Bahaj, Arda Durmaz, Mai Aly, Olisaemeka D. Ogbue, Hetty E. Carraway, Mikkael A. Sekeres, Valeria Visconte, Carmelo Gurnari, Jaroslaw P. Maciejewski
Meeting Abstract
Hematology
Fauzia Ullah, Danai Dima, Carmelo Gurnari, Suresh Kumar Balasubramanian, Olisaemeka Ogbue, Hussein Awada, Naomi Kawashima, Najiullah Omar, Swapna Thota, Hetty E. Carraway, Valeria Visconte, Jaroslaw P. Maciejewski
Article
Hematology
Amer M. Zeidan, Uwe Platzbecker, Jan Philipp Bewersdorf, Maximilian Stahl, Lionel Ades, Uma Borate, David Bowen, Rena Buckstein, Andrew Brunner, Hetty E. Carraway, Naval Daver, Maria Diez-Campelo, Theo de Witte, Amy E. DeZern, Fabio Efficace, Guillermo Garcia-Manero, Jacqueline S. Garcia, Ulrich Germing, Aristoteles Giagounidis, Elizabeth A. Griffiths, Robert P. Hasserjian, Eva Hellstrom-Lindberg, Marcelo Iastrebner, Rami Komrokji, Austin G. Kulasekararaj, Luca Malcovati, Yasushi Miyazaki, Olatoyosi Odenike, Valeria Santini, Guillermo Sanz, Phillip Scheinberg, Reinhard Stauder, Arjan A. van de Loosdrecht, Andrew H. Wei, Mikkael A. Sekeres, Pierre Fenaux
Summary: The initial response criteria developed by the International Working Group (IWG) in 2000 have limitations in their application to higher-risk MDS and their ability to fully capture the clinical benefits of novel investigational drugs. Therefore, an international panel of MDS experts used a modified Delphi process to develop consensus recommendations for updated response criteria that would be more reflective of patient-centered and clinically relevant outcomes. The updated criteria should lead to a better correlation between patient-centered outcomes and clinical trial results.
Article
Oncology
Yusuke Hara, Norio Shiba, Kenichi Yoshida, Genki Yamato, Taeko Kaburagi, Yuichi Shiraishi, Kentaro Ohki, Yusuke Shiozawa, Machiko Kawamura, Hirohide Kawasaki, Manabu Sotomatsu, Takumi Takizawa, Hidemasa Matsuo, Akira Shimada, Nobutaka Kiyokawa, Daisuke Tomizawa, Takashi Taga, Etsuro Ito, Keizo Horibe, Satoru Miyano, Souichi Adachi, Tomohiko Taki, Seishi Ogawa, Yasuhide Hayashi
Summary: In this study, TP53 and RB1 alterations were identified in pediatric AML patients through next-generation sequencing, and their prognostic implications were analyzed. The study also revealed the correlation between TP53 and RB1 alterations and low survival rates in non-core-binding factor AML patients. This research contributes to the development of risk-stratified therapy and precision medicine in pediatric AML.
GENES CHROMOSOMES & CANCER
(2023)
Article
Biochemistry & Molecular Biology
Yuichi Shiraishi, Junji Koya, Kenichi Chiba, Ai Okada, Yasuhito Arai, Yuki Saito, Tatsuhiro Shibata, Keisuke Kataoka
Summary: We introduce nanomonsv, a novel software for detecting somatic structural variations (SVs) using tumor and matched control long-read sequencing data with single-base resolution. It includes two detection modules: Canonical SV module and Single breakend SV module. Our approaches demonstrate higher precision and recall in identifying somatic SVs compared to existing methods, and enable the classification and analysis of various features of SVs, providing insights into mutational processes and functional consequences.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Oncology
Franziska Briest, Daniel Noerenberg, Cornelius Hennch, Kenichi Yoshida, Raphael Hablesreiter, Jose Nimo, Daniel Sasca, Marieluise Kirchner, Larry Mansouri, Yoshikage Inoue, Laura Wiegand, Annette M. Staiger, Beatrice Casadei, Penelope Korkolopoulou, January Weiner, Armando Lopez-Guillermo, Arne Warth, Tamas Schneider, Akos Nagy, Wolfram Klapper, Michael Hummel, George Kanellis, Ioannis Anagnostopoulos, Philipp Mertins, Lars Bullinger, Richard Rosenquist, Theodoros P. Vassilakopoulos, German Ott, Seishi Ogawa, Frederik Damm
Summary: Recent exome-wide studies have found frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. The functional consequences of ZNF217 alterations were comprehensively evaluated in PMBCL, and it was found that these alterations led to changes in cytokine and interferon signal transduction, disturbed expression of certain genes, altered cell behavior, and aberrant differentiation. ZNF217 was also discovered to act within a histone modifier complex and interfere with chromatin structure.
Article
Multidisciplinary Sciences
Tomomi Nishimura, Nobuyuki Kakiuchi, Kenichi Yoshida, Takaki Sakurai, Tatsuki R. R. Kataoka, Eiji Kondoh, Yoshitsugu Chigusa, Masahiko Kawai, Morio Sawada, Takuya Inoue, Yasuhide Takeuchi, Hirona Maeda, Satoko Baba, Yusuke Shiozawa, Ryunosuke Saiki, Masahiro M. M. Nakagawa, Yasuhito Nannya, Yotaro Ochi, Tomonori Hirano, Tomoe Nakagawa, Yukiko Inagaki-Kawata, Kosuke Aoki, Masahiro Hirata, Kosaku Nanki, Mami Matano, Megumu Saito, Eiji Suzuki, Masahiro Takada, Masahiro Kawashima, Kosuke Kawaguchi, Kenichi Chiba, Yuichi Shiraishi, Junko Takita, Satoru Miyano, Masaki Mandai, Toshiro Sato, Kengo Takeuchi, Hironori Haga, Masakazu Toi, Seishi Ogawa
Summary: Recent studies have shown that clones carrying common cancer mutations frequently evolve in normal tissues, but we still lack knowledge about the additional driver events that occur before these clones evolve into cancer. In this study, using phylogenetic analyses, we found unique evolutionary histories in breast cancers with der(1;16), a common driver alteration. The timing of early evolutionary events was estimated and showed that both cancer and non-cancer clones evolved from a common ancestor in the patient's early 30s. Multiple independent cancer founders from non-cancer ancestors were also observed, contributing to intratumor heterogeneity. These findings provide new insights into the evolution of breast cancer.
Article
Oncology
Eirini Giannakopoulou, Madeleine Lehander, Stina Virding Culleton, Weiwen Yang, Yingqian Li, Terhi Karpanen, Tetsuichi Yoshizato, Even H. Rustad, Morten Milek Nielsen, Ravi Chand Bollineni, Trung T. Tran, Marina Delic-Sarac, Thea Johanne Gjerdingen, Karolos Douvlataniotis, Maarja Laos, Muhammad Ali, Amy Hillen, Stefania Mazzi, Desmond Wai Loon Chin, Adi Mehta, Jeppe Sejero Holm, Amalie Kai Bentzen, Marie Bill, Marieke Griffioen, Tobias Gedde-Dahl, Soren Lehmann, Sten Eirik W. Jacobsen, Petter S. Woll, Johanna Olweus
Summary: The study identifies a T cell receptor reactive against a driver mutation in FLT3 in acute myeloid leukemia and demonstrates the efficacy of engineered T cells against this mutation in immunotherapy.
Meeting Abstract
Oncology
Sudipto Mukherjee, Weichuan Dong, Aaron T. Gerds, Hetty E. Carraway, Abhay Singh, Anjali S. Advani, Siran M. Koroukian
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Oncology
Asami Yamada, Jun-ichirou Yasunaga, Lihan Liang, Wenyi Zhang, Junya Sunagawa, Shinji Nakaoka, Shingo Iwami, Yasunori Kogure, Yuta Ito, Keisuke Kataoka, Masanori Nakagawa, Masako Iwanaga, Atae Utsunomiya, Ki-Ryang Koh, Toshiki Watanabe, Kisato Nosaka, Masao Matsuoka
Summary: This study demonstrates that profiling the humoral immunity to HTLV-1 antigens and measuring proviral load can be used to classify disease status and predict the development of HTLV-1-associated diseases. The study also highlights the importance of anti-Gag proteins in disease prognosis.
Letter
Oncology
Tomas Radivoyevitch, Robert Peter Gale, Matt E. Kalaycio
Meeting Abstract
Oncology
Farhad Ravandi-Kashani, Ashwin Kishtagari, Hetty Carraway, Emily Curran, Gary Schiller, Alex Cacovean, Bhagyashree Yadav, Thomas Butler, Jeffrey Lancet
