Article
Cell Biology
Sophie Broadway-Stringer, He Jiang, Kirsty Wadmore, Charlotte Hooper, Gillian Douglas, Violetta Steeples, Amar J. Azad, Evie Singer, Jasmeet S. Reyat, Frantisek Galatik, Elisabeth Ehler, Pauline Bennett, Jacinta I. Kalisch-Smith, Duncan B. Sparrow, Benjamin Davies, Kristina Djinovic-Carugo, Mathias Gautel, Hugh Watkins, Katja Gehmlich
Summary: Pathogenic variants in ACTN2 gene have been identified as rare causes of Hypertrophic Cardiomyopathy. However, the underlying disease mechanisms are not well understood. This study found that a missense variant in alpha-actinin renders the protein less stable, leading to molecular and morphological abnormalities in mouse hearts.
Article
Multidisciplinary Sciences
E-Wei Tan, Kek Heng Chua, Sherry Usun Jones, Lay Koon Tan, Alexander Loch, Boon Pin Kee
Summary: This study investigated 152 cardiomyopathy patients and found a different genetic composition in Malaysian patients compared to Western populations, with only one patient carrying a mutation in the MYH7 gene. The finding suggests the need for a more comprehensive mutation study on Malaysian cardiomyopathy patients to better understand the genetic causes of cardiomyopathy in Malaysia.
Article
Multidisciplinary Sciences
Yasuhide Kuwabara, Allen J. York, Suh-Chin Lin, Michelle A. Sargent, Kelly M. Grimes, James P. Pirruccello, Jeffery D. Molkentin
Summary: We identified a variant in the FLII gene that is associated with cardiac remodeling in heart disease. Further studies showed that Flii protein binds to sarcomeric actin thin filament and affects its length. Deletion of Flii or introduction of the R1245H amino acid substitution in mice resulted in cardiomyopathy due to shortening of actin thin filaments. The FLII variant increases the risk of cardiomyopathy by altering sarcomere structure and contractile dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Genetics & Heredity
Yanqing Zhang, Haozheng Zhang, Wei Wu, Dong Wang, Yuqiang Lv, Dongmei Zhao, Lingxiao Wang, Yi Liu, Kaihui Zhang
Summary: This study reported the first case of Luscan-Lumish syndrome (LLS) caused by a SETD2 gene mutation in China. The clinical and genetic features of the patient were described in detail. The results of this study enriched the mutation spectrum of the SETD2 gene and deepened the understanding of the disease.
FRONTIERS IN GENETICS
(2023)
Article
Endocrinology & Metabolism
Naama Pollack-Schreiber, Benjamin Udoka Nwosu, Parissa Salemi
Summary: The frequent misdiagnosis of MODY subtypes emphasizes the importance of clarifying the clinical spectrum of the disease phenotypes in suspected subjects for accurate diagnosis and management plans. This case report illustrates the identification of a gene variant in the HNF1A gene, initially reported as a variant of uncertain significance and later upgraded to a likely pathogenic variant. It provides valuable clinical information and management approaches for the wider scientific community.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Dan Zhou, Dongmei Yu, Jeremiah M. Scharf, Carol A. Mathews, Lauren McGrath, Edwin Cook, S. Hong Lee, Lea K. Davis, Eric R. Gamazon
Summary: Research has revealed the significant roles of common small-effect polygenic burden and large-effect variants in the genetic basis of complex traits. Studies have shown that it is possible to quantify the power to detect a lower PB in LEV carriers compared to non-carriers through simulations.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jeeyeon Lee, Ji Yeon Ham, Ho Yong Park, Jin Hyang Jung, Wan Wook Kim, Byeongju Kang, Yee Soo Chae, Soo Jung Lee, In Hee Lee, Nan Young Lee
Summary: The pathogenic variant of the BRCA1/2 gene is strongly associated with hereditary breast or ovarian cancer, making it important to screen blood relatives for genetic testing. This study assessed the feasibility of targeted cascade genetic testing for family members of BRCA1/2 gene carriers and found that it can determine the PV or LPV status of the gene.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Kiran Krishnamachari, Dylan Lu, Alexander Swift-Scott, Anuar Yeraliyev, Kayla Lee, Weitai Huang, Sim Ngak Leng, Anders Jacobsen Skanderup
Summary: The authors develop VarNet, a weakly supervised deep learning model for somatic variant calling in cancer with robust performance across multiple cancer genomics datasets.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Barbara Oliveira-Mendes, Sylvain Feliciangeli, Melissa Menard, Frank Chatelain, Malak Alameh, Jerome Montnach, Sebastien Nicolas, Beatrice Ollivier, Julien Barc, Isabelle Baro, Jean-Jacques Schott, Vincent Probst, Florence Kyndt, Isabelle Denjoy, Florian Lesage, Gildas Loussouarn, Michel De Waard
Summary: This study aims to standardize and accelerate the phenotyping process of KCNH2 genetic variants to aid in clinical diagnosis and patient counseling. By developing new biophysical protocols and structural evaluations, three novel pathogenicity indexes were defined.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Immunology
Hongling Jia, Hui Wang, Lan Cao, Zhisheng Lai, Zichun Cheng, Qingpei Chen, Tongzheng Liu, Xiangyi Liu, Yanting Wen, Conghui Xu, Weizhi Lu, Guang Yang, Deqian Zhou, Biao Di, Feng Gao, Zhicong Yang
Summary: Since its first reported in South Africa, the SARS-CoV-2 Omicron variant has rapidly spread to over 100 countries. China recently identified only two cases infected with the Omicron variant. The patient in Guangzhou has a longer incubation period and mild symptoms. Analysis of the viral genome sequence reveals three missing unique Omicron mutations and one additional mutation in the newly characterized genome. These unique mutations may be related to the clinical presentation in this case.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Multidisciplinary Sciences
May E. Montasser, Cristopher V. Van Hout, Lawrence Miloscio, Alicia D. Howard, Avraham Rosenberg, Myrasol Callaway, Biao Shen, Ning Li, Adam E. Locke, Niek Verweij, Tanima De, Manuel A. Ferreira, Luca A. Lotta, Aris Baras, Thomas J. Daly, Suzanne A. Hartford, Wei Lin, Yuan Mao, Bin Ye, Derek White, Guochun Gong, James A. Perry, Kathleen A. Ryan, Qing Fang, Gannie Tzoneva, Evangelos Pefanis, Charleen Hunt, Yajun Tang, Lynn Lee, Carole Sztalryd-Woodle, Braxton D. Mitchell, Matthew Healy, Elizabeth A. Streeten, Simeon Taylor, Jeffrey R. O'Connell, Aris N. Economides, Giusy Della Gatta, Alan R. Shuldiner
Summary: Increased blood levels of LDL-C and fibrinogen are independent risk factors for cardiovascular disease. A missense variant in the B4GALT1 gene was associated with lower LDL-C and fibrinogen levels, as well as decreased risk of coronary artery disease. This suggests that targeting protein galactosylation could be a potential therapeutic approach for reducing cardiovascular disease risk.
Article
Biochemistry & Molecular Biology
Kendal Prill, Michael R. Jones, Karl Steffensen, Grace Zi Teng, John F. Dawson
Summary: Many therapeutics for cardiomyopathy only alleviate symptoms without addressing the underlying mechanism. The onset of cardiomyopathy is believed to involve changes in calcium sensitivity and myosin activity. Trifluoperazine (TFP), a compound that binds troponin and other components of the calcium pathway, was studied to evaluate its impact on calcium regulation and heart function. In vitro experiments showed that TFP increased cardiac actomyosin activity while in vivo experiments using embryonic zebrafish demonstrated elevated heart rates with effective drug concentrations. In silico modeling suggested structural changes in troponin that could affect protein interactions within thin filaments and therefore impact heart function regulation.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Genetics & Heredity
Cesare Rossi, Sherin Ramadan, Cecilia Evangelisti, Simona Ferrari, Maria Accadia, Reha M. Toydemir, Emanuele Panza
Summary: In this study, a novel pathogenetic variant affecting splicing in the CHD7 gene, c.5607+17A > G, was identified. Through the construction of minigenes using exon trapping vectors, the molecular effect of the variant on CHD7 gene splicing was characterized. The findings were confirmed using cDNA synthesized from RNA extracted from patient lymphocytes, and the alteration of splicing was shown to be due to the generation of a recognition motif for the recruitment of a splicing effector.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Nikolay A. Barashkov, Fedor A. Konovalov, Tuyara V. Borisova, Fedor M. Teryutin, Aisen V. Solovyev, Vera G. Pshennikova, Nadejda V. Sapojnikova, Lyubov S. Vychuzhina, Georgii P. Romanov, Nyurgun N. Gotovtsev, Igor V. Morozov, Alexander A. Bondar, Fedor A. Platonov, Tatiana E. Burtseva, Elza K. Khusnutdinova, Olga L. Posukh, Sardana A. Fedorova
Summary: A novel pathogenic variant related to the FYCO1 gene was identified in the Yakut population of Eastern Siberia, highlighting the region as having the most extensive accumulation of this unique mutation. This finding sheds significant light on the genetic basis of congenital cataracts among the Yakut people.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Medicine, General & Internal
Varun Kaushik, John-Paul Plazzer, Ingrid Winship, Finlay Macrae
Summary: This article discusses the importance of genetic variant interpretation, using the relationship between mismatch repair gene variations and Lynch syndrome as an example to illustrate the role of genetic variant interpretation in the diagnosis and management of hereditary disorders.
INTERNAL MEDICINE JOURNAL
(2021)