Article
Oncology
Migle Gabrielaite, Mathias Husted Torp, Malthe Sebro Rasmussen, Sergio Andreu-Sanchez, Filipe Garrett Vieira, Christina Bligaard Pedersen, Savvas Kinalis, Majbritt Busk Madsen, Miyako Kodama, Guel Sude Demircan, Arman Simonyan, Christina Westmose Yde, Lars Ronn Olsen, Rasmus L. Marvig, Olga ostrup, Maria Rossing, Finn Cilius Nielsen, Ole Winther, Frederik Otzen Bagger
Summary: Copy-number variations (CNVs) have significant clinical implications for various diseases and cancers, but detecting relevant CNVs accurately remains challenging. Our study found diverse performance levels among different CNV calling tools, suggesting that combining the best tools could be a potential solution.
Article
Genetics & Heredity
Xiaojun Chen, Fatao Liu, Zin Mar Aung, Yan Zhang, Gang Chai
Summary: Hemifacial microsomia (HFM) is a rare congenital disease characterized by a spectrum of craniomaxillofacial malformations. This study identified rare germline mutations in HFM patients, with disruptions in signaling pathways potentially contributing to the disease. Further research is needed to fully understand the causative genes and mechanisms behind HFM.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Ning-Yuan Lee, Melissa Hum, Pei-Yi Ong, Matthew Khine Myint, Enya H. W. Ong, Kar-Perng Low, Zheng Li, Boon-Cher Goh, Joshua K. Tay, Kwok-Seng Loh, Melvin L. K. Chua, Soo-Chin Lee, Chiea-Chuen Khor, Ann S. G. Lee
Summary: This study aimed to identify germline genetic variants associated with an increased risk of developing nasopharyngeal carcinoma (NPC). Through sequencing DNA samples from Singaporean NPC patients, the study found 17 pathogenic variants enriched in NPC patients as compared to unaffected controls. Five of these variants were supported by repeated testing on an independent set of Singaporean NPC patients and controls. The study also identified the association between specific genes (JAK2, PRDM16, LRP1B, NIN, and NKX2-1) and NPC risk. Pathway analysis revealed a higher frequency of germline mutations in endocytosis and immune-modulating pathways. Overall, this research provides important insights into the genetic predisposition of NPC.
Article
Biochemistry & Molecular Biology
Yaxuan Liu, Hafdis T. Helgadottir, Pedram Kharaziha, Jungmin Choi, Francesc Lopez-Giraldez, Shrikant M. Mane, Veronica Hoiom, Carl Christofer Juhlin, Catharina Larsson, Svetlana Bajalica-Lagercrantz
Summary: This study aimed to identify new predisposing genes for hereditary breast cancer (HBC) using whole-exome sequencing, but no pathogenic variants in known hereditary cancer-related genes were found. Further analysis suggested that a combination of low- and intermediate-genetic-risk variants might contribute to breast cancer susceptibility in these families.
Article
Endocrinology & Metabolism
Maria Savvateeva, Anna Kudryavtseva, Elena Lukyanova, Anastasiya Kobelyatskaya, Vladislav Pavlov, Maria Fedorova, Elena Pudova, Zulfiya Guvatova, Dmitry Kalinin, Alexander Golovyuk, Elizaveta Bulavkina, Irina Katunina, George Krasnov, Anastasiya Snezhkina
Summary: This study analyzed somatic mutation profiles in HNPGLs and found that most patients had germline and somatic variants in paraganglioma susceptibility genes or related genes. The study also identified six significantly mutated genes and four mutational signatures associated with HNPGLs. These findings provide important insights into the molecular mechanisms involved in the development of HNPGLs.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Genetics & Heredity
Pedro Guimaraes de Azevedo, Maria de Lourdes Rabelo Guimaraes, Anna Luiza Braga Albuquerque, Rayane Benfica Alves, Bianca Gomes Fernandes, Flavia Marques de Melo, Raony Guimaraes Correa Do Carmo Lisboa Cardenas, Eitan Friedman, Luiz De Marco, Luciana Bastos-Rodrigues
Summary: This study investigated the genetic variants in two Brazilian families with obstructive sleep apnea syndrome (OSAS) that followed a seemingly autosomal dominant inheritance pattern. Whole exome sequencing identified variants in COX20, PTPDC1, and TMOD4 genes as strong candidate genes associated with OSAS phenotype in these families. Further studies are needed to confirm the contribution of these variants in a larger and more diverse population of OSAS cases.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Arisa Ueki, Kokichi Sugano, Kumiko Misu, Eriko Aimono, Kohei Nakamura, Shigeki Tanishima, Nobuyuki Tanaka, Shuji Mikami, Akira Hirasawa, Miho Ando, Teruhiko Yoshida, Mototsugu Oya, Hiroshi Nishihara, Kenjiro Kosaki
Summary: This case report describes a young-onset renal cell carcinoma (RCC) caused by a genomic FH deletion diagnosed through clinical sequencing. Despite the absence of a family history or skin tumors, the patient exhibited aggressive clinical features and a pathological diagnosis of FH-deficient RCC, suggesting a possible germline FH variant.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Faidon-Nikolaos Tilemis, Nikolaos M. Marinakis, Danai Veltra, Maria Svingou, Kyriaki Kekou, Anastasios Mitrakos, Maria Tzetis, Konstantina Kosma, Periklis Makrythanasis, Joanne Traeger-Synodinos, Christalena Sofocleous
Summary: The integration of whole-exome sequencing (WES) and sensitive bioinformatic tools has enabled the detection of copy number variants (CNVs) in patients with rare diseases (RDs), improving the diagnostic yield of WES.
Article
Medicine, General & Internal
Maryam Eghbali, Sara Cheraghi, Sara Samanian, Iman Rad, Jafar Meghdadi, Hamideh Akbari, Maryam Honardoost
Summary: This study identified a novel ARMC5 gene variant that is likely responsible for familial PMAH in Iranians. The identified variant may damage the function of the ARMC5 protein. Genetic testing can be used for early diagnosis of PMAH.
Article
Plant Sciences
Hisashi Udagawa, Hiroyuki Ichida, Takanori Takeuchi, Tomoko Abe, Yoshimitsu Takakura
Summary: In this study, a whole-exome sequencing (WES) procedure was developed in tobacco to characterize EMS-induced mutations in a test population, revealing a high number of single nucleotide variants. The amount of mutations detected by WES was 93.5% of those detected by whole-genome sequencing, while requiring significantly less sequencing data, making it a cost-effective tool for high-throughput mutation identification in tobacco.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Medicine, Research & Experimental
Lee-Moay Lim, Wen-Yu Chung, Daw-Yang Hwang, Chih-Chuan Yu, Hung-Lung Ke, Peir-In Liang, Ting-Wei Lin, Siao Muk Cheng, A-Mei Huang, Hung-Tien Kuo
Summary: This study compares the genetic alterations in urothelial carcinoma (UC) developed after kidney transplantation (UCKT) and in UC in patients on hemodialysis (UCHD). Specific gene mutations were found in UCKT, potentially contributing to the understanding of the molecular pathogenesis of urothelial carcinoma.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Lanlan Wang, Yali Ma, Wenjie Han, Qiumin Yang, Muhammad Jamil
Summary: By performing Whole Exome Sequencing (WES) on Pakistani lung cancer patients, this study identified clinically important pathogenic mutations in 6 DNA repair genes and revealed their potential implications on prognosis. Down-regulation of these mutated genes and hypermethylation in their promoters were observed, indicating a potential convergence of genetic and epigenetic factors driving genomic instability in lung cancer cells. These findings contribute to our understanding of lung cancer susceptibility and offer potential avenues for targeted therapeutic interventions in Pakistani patients.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Obstetrics & Gynecology
Stephanie Cheung, Philip Xie, Zev Rosenwaks, Gianpiero D. Palermo
Summary: The study aimed to identify specific germline mutations related to sperm reproductive competence in couples with unexplained infertility. The study found differences in sperm aneuploidy and gene mutation profiles between couples with successful and unsuccessful intracytoplasmic sperm injection outcomes. Rating: 9/10
FERTILITY AND STERILITY
(2023)
Article
Pediatrics
Triantafyllia Brozou, Layal Yasin, Danielle Brandes, Daniel Picard, Carolin Walter, Julian Varghese, Martin Dugas, Ute Fischer, Arndt Borkhardt, Oskar A. Haas
Summary: Molecular screening tools have simplified the evaluation of potential inherited susceptibility factors in pediatric malignancies. Whole exome trio analysis revealed 458 de novo variants, with 5 of them being cancer predisposing alterations. The rate of de novo variants increased with fathers' age, suggesting a potential correlation.
FRONTIERS IN PEDIATRICS
(2023)
Article
Genetics & Heredity
Eva Tosco-Herrera, Adrian Munoz-Barrera, David Jaspez, Luis A. Rubio-Rodriguez, Alejandro Mendoza-Alvarez, Hector Rodriguez-Perez, Jonathan Jou, Antonio Inigo-Campos, Almudena Corrales, Laura Ciuffreda, Francisco Martinez-Bugallo, Carol Prieto-Morin, Victor Garcia-Olivares, Rafaela Gonzalez-Montelongo, Jose Miguel Lorenzo-Salazar, Itahisa Marcelino-Rodriguez, Carlos Flores
Summary: This study assessed the performance of different tools in prioritizing germline causal variants in whole-exome sequencing (WES) data. Exomiser performed best in the top first rankings, while LIRICAL led in the top fifth rankings. Xrare had the highest diagnostic yield based on the more conservative top 10th rankings.
Article
Endocrinology & Metabolism
Ayanthi Wijewardene, Jeremy Hoang, Aung Min Maw, Matti Gild, Lyndal Tacon, Paul Roach, Geoffrey Schembri, David Chan, Roderick Clifton-Bligh
Summary: In this study, a new scoring system (I-PET) combining whole body scan (WBS) and FDG findings was proposed to identify patients who are refractory to radioactive iodine in thyroid cancer. The results showed that patients with I-PET [3B] were more likely to receive multikinase inhibitor therapy and had a higher mortality rate.
CLINICAL ENDOCRINOLOGY
(2023)
Review
Genetics & Heredity
Courtney K. Wallingford, Hannah Kovilpillai, Chris Jacobs, Erin Turbitt, Clare A. Primiero, Mary-Anne Young, Deanna G. Brockman, H. Peter Soyer, Aideen M. McInerney-Leo, Tatiane Yanes
Summary: This study reviewed current models for communicating polygenic scores (PGS) and psycho-behavioral outcomes. A total of 28 articles representing 17 studies were included. The study found limited consistency in PGS communication and evaluation of outcomes. Most studies presented risk in multiple ways and provided personalized lifestyle advice. The findings suggest the need for standardized guidelines and evidence-based interventions informed by behavior change theories.
GENETICS IN MEDICINE
(2023)
Article
Rheumatology
Lauren K. Ridley, Mark C. Hwang, John D. Reveille, Lianne S. Gensler, Mariko L. Ishimori, Matthew A. Brown, Mohammad H. Rahbar, Amirali Tahanan, Michael M. Ward, Michael H. Weisman, Thomas J. Learch
Summary: This study investigated a subgroup of patients with ankylosing spondylitis (AS) who had long-standing disease and fused sacroiliac (SI) joints and found that females and males with early symptom onset had less radiographic damage in the SI joints. All 23 patients without syndesmophytes were HLA-B27 positive.
JOURNAL OF RHEUMATOLOGY
(2023)
Article
Immunology
Zaied Ahmed Bhuyan, M. Arifur Rahman, Muralidhara Rao Maradana, Ahmed M. Mehdi, Anne-Sophie Bergot, Davide Simone, Marya El-Kurdi, Jose Garrido-Mesa, Cheng Bang Benjamin Cai, Amy J. Cameron, Aimee L. Hanson, Hendrik J. Nel, Tony Kenna, Paul Leo, Linda Rehaume, Matthew A. Brown, Francesco Ciccia, Ranjeny Thomas
Summary: Loss-of-function variants in RUNX3 are associated with ankylosing spondylitis (AS) and lead to immune dysregulation, intestinal dysbiosis, and inflammation. In AS, CD4-IEL cells and CD4+CD8+ T cells are decreased, while Treg cells are increased. TCR signaling dysfunction plays a role in the intestinal T-cell immunodeficiency observed in AS.
CLINICAL IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Xinyuan Zhang, Adewale S. Adebayo, Dongmeng Wang, Yasrab Raza, Max Tomlinson, Hannah Dooley, Ruth C. E. Bowyer, Kerrin S. Small, Claire J. Steves, Tim D. Spector, Emma L. Duncan, Alessia Visconti, Mario Falchi
Summary: Proton pump inhibitors (PPIs) are commonly used drugs in the UK. The use of PPIs has been linked to decreased bone mineral density (BMD) and increased fracture risk, but the findings have been inconsistent. This study explored the potential mechanisms behind PPI's impact on BMD and found that it may affect total hip BMD through both direct and indirect pathways, possibly involving metabolites related to the sex hormone pathway.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Biology
Nathan J. Cheetham, Milla Kibble, Andrew Wong, Richard J. Silverwood, Anika Knuppel, Dylan M. Williams, Olivia K. L. Hamilton, Paul H. Lee, Charis Bridger Staatz, Giorgio Di Gessa, Jingmin Zhu, Srinivasa Vittal Katikireddi, George B. Ploubidis, Ellen J. Thompson, Ruth C. E. Bowyer, Xinyuan Zhang, Golboo Abbasian, Maria Paz Garcia, Deborah Hart, Jeffrey Seow, Carl Graham, Neophytos Kouphou, Sam Acors, Michael H. Malim, Ruth E. Mitchell, Kate Northstone, Daniel Major-Smith, Sarah Matthews, Thomas Breeze, Michael Crawford, Lynn Molloy, Alex S. F. Kwong, Katie Doores, Nishi Chaturvedi, Emma L. Duncan, Nicholas J. Timpson, Claire J. Steves
Summary: This study found that antibody levels against SARS-CoV-2 can be used to evaluate immune responses and predict the risk of future infection. Higher antibody levels are associated with increased protection against future infections. The study also demonstrated that a third dose of the vaccine can increase antibody levels and reduce disparities compared to earlier vaccinations.
Review
Oncology
B. W. M. Thilini J. Basnayake, Paul Leo, Sudha Rao, Sarju Vasani, Lizbeth Kenny, Nikolas K. K. Haass, Chamindie Punyadeera
Summary: Head and neck cancers (HNC) are a heterogeneous group of malignancies arising in various anatomical sites within the head and neck region. Patient-derived cancer organoids, or tumouroids, have been developed as in vitro model systems that replicate in vivo tumor characteristics. These tumouroids can play an essential role in bringing precision medicine for highly heterogeneous cancer types such as HNC.
BRITISH JOURNAL OF CANCER
(2023)
Article
Dermatology
Courtney K. Wallingford, Anastassia Demeshko, Asha Krishnankutty Krishnakripa, Darren J. Smit, David L. Duffy, Brigid Betz-Stablein, Annette Pflugfelder, Kasturee Jagirdar, Elizabeth Holland, Graham J. Mann, Clare A. Primiero, Tatiane Yanes, Josep Malvehy, Celia Badenas, Cristina Carrera, Paula Aguilera, Catherine M. Olsen, Sarah Ward, Nikolas K. Haass, Richard A. Sturm, Susana Puig, David C. Whiteman, Matthew H. Law, Anne E. Cust, Miriam Potrony, H. Peter Soyer, Aideen M. McInerney-Leo
Summary: Genetic characterization can improve cost-effectiveness of melanoma screening. The interactions between MC1R RHC variants and MITF E318K in melanoma risk have not been well explored. This study found that while all MC1R RHC genotypes increase melanoma risk in E318K(-) individuals, only the MC1R R genotype increases melanoma risk in E318K(+) individuals.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Editorial Material
Oncology
Karel Pacak, Roderick Clifton-Bligh
Summary: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors that produce catecholamines. Recent advances in their management, localization, treatment, and surveillance have significantly improved outcomes for patients with PPGLs or carriers of pathogenic genetic variants linked to these tumors. Molecular stratification, revised definitions, specific clinical features, plasma biomarkers, imaging techniques, treatment guidelines, and international consensus play important roles in enhancing understanding and future interventions for PPGLs.
ENDOCRINE-RELATED CANCER
(2023)
Article
Oncology
Dahlia F. Davidoff, Eugenie S. Lim, Diana E. Benn, Yuvanaa Subramaniam, Eleanor Dorman, John R. Burgess, Scott A. Akker, Roderick J. Clifton-Bligh
Summary: Phaeochromocytoma and paraganglioma are highly heritable tumours, often caused by mutations in Krebs's cycle genes such as succinate dehydrogenase (SDH). This study found evidence of transmission ratio distortion (TRD) in the transmission of SDHB and SDHD pathogenic variants, suggesting a departure from Mendelian inheritance. The reasons for TRD and its implications for reproductive counseling and further research were discussed.
ENDOCRINE-RELATED CANCER
(2023)
Review
Oncology
Susan Richter, Timothy J. Garrett, Nicole Bechmann, Roderick J. Clifton-Bligh, Hans K. Ghayee
Summary: Metabolites play a crucial role in maintaining life and can be quantified to improve the diagnosis and treatment of pheochromocytoma/paraganglioma (PPGL). PPGLs have unique features that provide biomarkers and clues for targeted treatments. Genetic aberrations in PPGL alter cellular pathways and can be exploited diagnostically. Personalized diagnostics and treatment are within reach with the availability of omics technologies.
ENDOCRINE-RELATED CANCER
(2023)
Article
Biochemistry & Molecular Biology
Jane Tiller, Andrew Bakshi, Grace Dowling, Louise Keogh, Aideen McInerney-Leo, Kristine Barlow-Stewart, Tiffany Boughtwood, Penny Gleeson, Martin B. Delatycki, Ingrid Winship, Margaret Otlowski, Paul Lacaze
Summary: Concerns about genetic discrimination in life insurance hinder Australians from undergoing genetic testing. A partial, self-regulated moratorium was introduced by the life insurance industry, but most respondents were unaware of its legality and believed that federal legislation is needed to regulate this issue.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Endocrinology & Metabolism
Neelam Hassan, Celia L. L. Gregson, Haotian Tang, Marc van der Kamp, Paul Leo, Aideen M. McInerney-Leo, Jie Zheng, Maria Luisa Brandi, Jonathan C. Y. Tang, William Fraser, Michael D. Stone, Elin Grundberg, Matthew A. Brown, Emma L. Duncan, Jonathan H. Tobias
Summary: Rare heterozygous loss-of-function variants in the GALNT3 gene may cause osteoporosis without altering phosphate concentration. These findings suggest that GALNT3 may affect bone mineral density through pathways other than FGF23 regulation, providing potential novel drug targets for osteoporosis.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Laura A. Magee, Erika Molteni, Vicky Bowyer, Jeffrey N. Bone, Harriet Boulding, Asma Khalil, Hiten D. Mistry, Lucilla Poston, Sergio A. Silverio, Ingrid Wolfe, Emma L. Duncan, Peter von Dadelszen
Summary: Among women of reproductive age, older age, White ethnicity, and being in the least-deprived index of multiple deprivation are independently associated with higher vaccine uptake. Ethnicity has the strongest influence, while multiple deprivation has the weakest. These findings are crucial for informing future vaccination policies and public messaging.
NATURE COMMUNICATIONS
(2023)