Article
Genetics & Heredity
Jianlong Zhuang, Junyu Wang, Qi Luo, Shuhong Zeng, Yu'e Chen, Yuying Jiang, Xinying Chen, Yuanbai Wang, Yingjun Xie, Gaoxiong Wang, Chunnuan Chen
Summary: This study identifies an association between the CHRNA1 gene and lethal multiple pterygium syndrome (LMPS) in a Chinese family, expanding the mutation spectrum of the CHRNA1 gene.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Yumeilan Liu, Hao Chen, Hongping Cui
Summary: By analyzing two datasets, it was found that pterygium and primary Sjogren's Syndrome (pSS) have many similarities in clinical symptoms and ocular pathophysiological changes, but their etiology is unclear. The analysis of gene expression profiles revealed 14 upregulated genes that are associated with pathways related to virus infection, antigen processing and presentation, nuclear factor-kappa B, and Th17 cell differentiation. In the era of the COVID-19 epidemic, the relationship between virus infection, vaccination, and the incidence of pSS and pterygium growth deserves more attention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Amit K. Tiwari, Varunvenkat M. Srinivasan, Shubha R. Phadke, Deepti Saxena
Summary: We report the third case of FADS caused by biallelic DOK7 variants, which strengthens the association between DOK7 and this lethal phenotype and also highlights the lack of genotype-phenotype correlation.
Review
Genetics & Heredity
Isabel Filges, Stephanie Juenemann, Elke Viehweger, Sevgi Tercanli
Summary: Arthrogryposis, or arthrogryposis multiplex congenita, is a term used to describe conditions with multiple congenital contractures. It has a diverse range of causes, with over 400 specific disorders identified so far. Early detection during pregnancy is important for counseling and management options, and we provide essential knowledge to increase awareness. However, interdisciplinary expert opinion is still necessary for individual cases.
PRENATAL DIAGNOSIS
(2023)
Article
Multidisciplinary Sciences
Peter H. Dixon, Adam P. Levine, Ines Cebola, Melanie M. Y. Chan, Aliya S. Amin, Anshul Aich, Monika Mozere, Hannah Maude, Alice L. Mitchell, Jun Zhang, Jenny Chambers, Argyro Syngelaki, Jennifer Donnelly, Sharon Cooley, Michael Geary, Kypros Nicolaides, Malin Thorsell, William M. Hague, Maria Cecilia Estiu, Hanns-Ulrich Marschall, Daniel P. Gale, Catherine Williamson
Summary: The study identified multiple genetic signals associated with intrahepatic cholestasis of pregnancy (ICP), shedding light on the disease which can lead to preterm birth and stillbirth. Common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements were pinpointed as contributing mechanisms to ICP susceptibility.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Feifei Wang, Dongzuo Liang, Yang Li, Shuangge Ma
Summary: Analyzing genetic data with limited sample size and high dimensionality is a challenge in biomedical research. We propose incorporating prior information and using a convolutional neural network to label textual information from previous studies, which improves the accuracy of integrative analysis of multiple genetic datasets. Our simulation studies show satisfactory performance and we further analyze data on skin cutaneous melanoma to establish practical utility.
Article
Multidisciplinary Sciences
Matthias Wuttke, Eva Koenig, Maria-Alexandra Katsara, Holger Kirsten, Saeed Khomeijani Farahani, Alexander Teumer, Yong Li, Martin Lang, Burulca Goecmen, Cristian Pattaro, Dorothee Guenzel, Anna Koettgen, Christian Fuchsberger
Summary: A genotype imputation approach was applied to whole exome sequencing data from the UK Biobank, resulting in the discovery of 158 rare variants and 105 genes significantly associated with kidney function traits. This approach boosts statistical power and provides a comprehensive resource for directing experimental and clinical studies of kidney disease.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Arianna Dal Buono, Laura Poliani, Luana Greco, Paolo Bianchi, Monica Barile, Valentina Giatti, Cristiana Bonifacio, Silvia Carrara, Alberto Malesci, Luigi Laghi
Summary: This study investigated the prevalence of germline mutations in cancer predisposition genes in patients with pancreatic ductal adenocarcinoma (PDAC) or suspected related hereditary syndromes. The results showed that 20.1% of the tested subjects carried at least one pathogenic variant in the genes of interest. Therefore, the incorporation of genetic testing and multiple-gene panels in the management of pancreatic cancer would be beneficial.
Article
Genetics & Heredity
Ebba Alkhunaizi, Nicole Martin, Angie C. Jelin, Mara Rosner, Diana J. Bailey, Laurie A. Steiner, Saquib Lakhani, Weizhen Ji, Philip J. Katzman, Katherine R. Forster, Olga Jarinova, Patrick Shannon, David Chitayat
Summary: Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition with a estimated incidence of 1 in 3000 live births, which can be acquired or caused by genetic disorders affecting various body systems. Molecular diagnosis plays a crucial role in prognosis, recurrence risk assessment, and reproductive options.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Caiyuan Chen, Jin Han, Jiaxin Xue, Ru Li, Guilan Chen, Xin Yang, Jiajie Tang, Fucheng Li, Dongzhi Li
Summary: This report presents two novel mutations of the CHRND gene, providing important insights into the genetic and phenotypic heterogeneity of Lethal multiple pterygium syndrome. It also demonstrates the use of prenatal diagnosis to measure the facial angle for determining micrognathia in the first trimester of pregnancy. Overall, this study expands our understanding of the disease and offers valuable recommendations for future pregnancies in affected families.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Noemi Dahan-Oliel, Klaus Dieterich, Frank Rauch, Ghalib Bardai, Taylor N. Blondell, Anxhela Gjyshi Gustafson, Reggie Hamdy, Xenia Latypova, Kamran Shazand, Philip F. Giampietro, Harold van Bosse
Summary: Multiple pterygium syndrome (MPS) is a rare genetic disorder characterized by joint contractures and webbing, necessitating molecular diagnosis and careful monitoring of the spine for management. Treatment of scoliosis in MPS patients includes bracing, serial spine casting, and potential non-fusion spinal instrumentation to modulate severe curves.
Article
Pediatrics
Xuliang Zhao, Xu Li, Weiwei Sun, Zhuojun Wei, Min Yu, Man Zhang, Ruixia Tian
Summary: This case report describes a fetus with major cardiac malformation caused by a novel mutation in the CTNND1 gene. It is the first reported case of fetal complex cardiac malformations caused by this CTNND1 mutation. The findings provide new clinical references for prenatal diagnosis and suggest an important role for CTNND1 in early cardiac development.
FRONTIERS IN PEDIATRICS
(2023)
Article
Endocrinology & Metabolism
Xiaojian Mao, Liangliang Tang, Hongyi Li, Wen Zhang, Li Liu, Heyong Wang, Abdalbari Headar
Summary: This study aims to explore the functions and gene sets of mutated genes related to hyperthyroidism in children. Through gene ontology and biological signaling pathway analysis, it was found that hormone activity and response to peptide hormone are the most significant gene ontology functions and thyroid hormone signaling pathway is the most significant biological signaling pathway. The identified mutated genes provide insights into the expected effects of multiple mutated genes on hyperthyroidism in children.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sheng-Hang Jiang, Huan-Huan Wang, Ren Zhang, Zhen-Yu Yang, Guo-Ren He, Feng Ming
Summary: Analysis of BF and WF transcriptomes reveals the key role of RhF3'H and RhGT74F2 in flower color formation. The study provides new insights into rose color formation and even blue rose formation.
PLANT MOLECULAR BIOLOGY
(2023)
Article
Medicine, General & Internal
Sumita Mehta, Ekta Kale, Tarun Kumar Ravi, Ankita Mann, Pratibha Nanda
Summary: Bartsocas-Papas Syndrome (BPS) is an extremely rare autosomal recessive syndrome characterized by craniofacial deformities, joint pterygia, limb abnormalities, and genital defects. The syndrome is typically lethal with most babies dying in utero or shortly after birth. Early antenatal diagnosis is crucial, especially in couples with consanguineous marriages or a positive family history.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH
(2021)
Review
Endocrinology & Metabolism
Bettina Winzeler, Nicola Tufton, Eugenie Lim, Ben G. Challis, Soo-Mi Park, Louise Izatt, Paul Carroll, Anand Velusamy, Tony Hulse, Benjamin C. Whitelaw, Ezequiel Martin, Fay Rodger, Melanie Maranian, Graeme R. Clark, Scott Akker, Eamonn R. Maher, Ruth T. Casey
Summary: This study investigated the clinical utility of somatic sequencing in a large cohort of patients with PPGL in the United Kingdom, finding that 32% of patients had a germline mutation and 26% had one or more driver somatic variants. Pathogenic somatic variants were most commonly identified in the VHL, NF1, HRAS, and RET genes, and somatic sequencing may be most informative for patients without a germline genetic driver.
CLINICAL ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Sophie T. Williams, Prodromos Chatzikyriakou, Paul V. Carroll, Barbara M. McGowan, Anand Velusamy, Gemma White, Rupert Obholzer, Scott Akker, Nicola Tufton, Ruth T. Casey, Eamonn R. Maher, Soo-Mi Park, Mary Porteous, Rebecca Dyer, Tricia Tan, Florian Wernig, Angela F. Brady, Monika Kosicka-Slawinska, Benjamin C. Whitelaw, Huw Dorkins, Fiona Lalloo, Paul Brennan, Joseph Carlow, Richard Martin, Anna L. Mitchell, Rachel Harrison, Lara Hawkes, John Newell-Price, Alan Kelsall, Rebecca Igbokwe, Julian Adlard, Schaida Schirwani, Rosemarie Davidson, Patrick J. Morrison, Teng-Teng Chung, Christopher Bowles, Louise Izatt
Summary: This study presents the largest cohort of 91 SDHC patients worldwide, showing that most patients primarily develop head and neck paraganglioma (HNPGL) disease, with a smaller proportion having extra-adrenal paraganglioma (EAPGL) and phaeochromocytomas (PCC), along with an increased risk of gastrointestinal stromal tumours (GIST) and renal cell cancers (RCC). About one fifth of the patients develop malignant disease, necessitating comprehensive lifelong tumor screening and surveillance.
CLINICAL ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Anthony McGuigan, James Whitworth, Avgi Andreou, Timothy Hearn, Marc Tischkowitz, Eamonn R. Maher
Summary: Multi-Locus Inherited Neoplasia Allele Syndrome (MINAS) refers to individuals with germline pathogenic variants in two or more cancer susceptibility genes (CSGs). As the use of exome/genome sequencing increases, the detection of MINAS is becoming more frequent. Most MINAS cases have a pathogenic variant in either BRCA1 or BRCA2, while other individual CSG combinations are rare. Some MINAS cases present unusual tumor phenotypes and multiple primary tumors, suggesting complex interactions between the relevant CSGs. Systematic reporting of MINAS cases can improve prognostic predictions for specific CSG combinations.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Alice Garrett, Chey Loveday, Laura King, Samantha Butler, Rachel Robinson, Carrie Horton, Amal Yussuf, Subin Choi, Beth Torr, Miranda Durkie, George J. Burghel, James Drummond, Ian Berry, Andrew Wallace, Alison Callaway, Diana Eccles, Marc Tischkowitz, Katrina Tatton-Brown, Katie Snape, Terri McVeigh, Louise Izatt, Emma R. Woodward, Nelly Burnichon, Anne-Paule Gimenez-Roqueplo, Francesco Mazzarotto, Nicola Whiffin, James Ware, Helen Hanson, Tina Pesaran, Holly LaDuca, Alexandre Buffet, Eamonn R. Maher, Clare Turnbull
Summary: The weight of evidence for the observation of rare missense variants in SDHB or SDHD in individuals with rare neuroendocrine tumors is uncertain. This study compared the frequency of these variants in cases of pheochromocytomas and paragangliomas (PCC/PGL) with population controls and calculated likelihood ratios for their pathogenicity. Regional enrichments of these variants and subphenotypic likelihood ratios were also measured. The study found that these rare missense variants can provide substantial evidence toward pathogenicity in PCC/PGL.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Alexander J. Thompson, Yousef M. Alwan, Vijay A. C. Ramani, D. Gareth Evans, Eamonn R. Maher, Emma R. Woodward
Summary: The purpose of this study was to determine the cost-effectiveness of annual renal imaging surveillance (RIS) in hereditary leiomyomatosis and renal cell cancer (HLRCC). The study found that annual contrast-enhanced renal MRI surveillance (CERMRIS) in HLRCC is cost-effective across different age groups.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Bryndis Yngvadottir, Avgi Andreou, Laia Bassaganyas, Alexey Larionov, Alex J. Cornish, Daniel Chubb, Charlie N. Saunders, Philip Smith, Huairen Zhang, Yasemin Cole, James Larkin, Lisa Browning, Samra Turajlic, Kevin Litchfield, Richard S. Houlston, Eamonn R. Maher
Summary: In unselected RCC patients, approximately 6% carry germline variants that require further follow-up analysis. Expanding the genomic panel for RCC susceptibility gene testing can improve diagnostic yield.
HUMAN MOLECULAR GENETICS
(2022)
Article
Genetics & Heredity
Helen Hanson, Miranda Durkie, Fiona Lalloo, Louise Izatt, Terri P. McVeigh, Jackie A. Cook, Carole Brewer, James Drummond, Samantha Butler, Treena Cranston, Ruth Casey, Tricia Tan, Daniel Morganstein, Diana M. Eccles, Marc Tischkowitz, Clare Turnbull, Emma Roisin Woodward, Eamonn R. Maher
Summary: SDHA PGV carriers are common in patients with paraganglioma and phaeochromocytoma, and the variant often presents as sporadic tumors in patients without family history. Studies show that the penetrance of SDHA-associated tumors is low, which poses challenges for surveillance and management.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Cell Biology
Zoe Markham-Lee, Neil Morgan, Jonas Emsley
Summary: ADAMTS13 is a plasma metalloprotease that cleaves VWF to maintain hemostasis, and its mutations are associated with Thrombotic Thrombocytopenic Purpura. Molecular characterization of ADAMTS13 is important for understanding the mechanisms of TTP.
Review
Genetics & Heredity
Fiona Jane Bruinsma, James G. Dowty, Aung Ko Win, Laura C. Goddard, Prachi Agrawal, Domenico Attina', Nabil Bissada, Monica De Luise, Daniel B. Eisen, Mitsuko Furuya, Giuseppe Gasparre, Maurizio Genuardi, Anne-Marie Gerdes, Thomas Van Overeem Hansen, Arjan C. Houweling, Paul Christiaan Johannesma, Andre Lencastre, Derek Lim, Noralane M. Lindor, Valentina Luzzi, Maeve Lynch, Antonella Maffe, Fred H. Menko, Guido Michels, Jose S. Pulido, Ryu H. Jay, Elke C. Sattler, Ortrud K. Steinlein, Sara Tomassetti, Kathy Tucker, Daniela Turchetti, Irma van de Beek, Lore van Riel, Maurice van Steensel, Thierry Zenone, Maurizo Zompatori, Jennifer Walsh, Davide Bondavalli, Eamonn R. Maher, Ingrid M. Winship
Summary: BHD syndrome is a rare genetic syndrome caused by FLCN gene variants, which can increase the risk of various manifestations including fibrofolliculomas, pulmonary cysts, pneumothorax, and renal cell carcinoma. This study provides updated penetrance estimates based on a large dataset, which are crucial for the genetic counseling and clinical management of BHD syndrome.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Larissa Bilo, Eguzkine Ochoa, Sunwoo Lee, Daniela Dey, Ingo Kurth, Florian Kraft, Fay Rodger, France Docquier, Ana Toribio, Leonardo Bottolo, Gerhard Binder, Gyoergy Fekete, Miriam Elbracht, Eamonn R. Maher, Matthias Begemann, Thomas Eggermann
Summary: Imprinting disorders (ImpDis) are caused by aberrant regulation of monoallelically and parent-of-origin-dependent expressed genes. This study aimed to investigate multilocus imprinting disturbances (MLIDs) in ImpDis patients using methylation data obtained from next-generation sequencing (ImprintSeq) and whole-exome sequencing (WES). The results showed that ImprintSeq has higher sensitivity in detecting mosaic imprinting defects in MLID patients, while WES failed to identify additional MLID causes.
CLINICAL EPIGENETICS
(2023)
Article
Genetics & Heredity
Janine Reurink, Nicole Weisschuh, Alejandro Garanto, Adrian Dockery, L. Ingeborgh van den Born, Isabelle Fajardy, Lonneke Haer-Wigman, Susanne Kohl, Bernd Wissinger, G. Jane Farrar, Tamar Ben-Yosef, Fatma Kivrak Pfiffner, Wolfgang Berger, Marianna E. Weener, Lubica Dudakova, Petra Liskova, Dror Sharon, Manar Salameh, Ashley Offenheim, Elise Heon, Giorgia Girotto, Paolo Gasparini, Anna Morgan, Arthur A. Bergen, Jacoline B. ten Brink, Caroline C. W. Klaver, Lisbeth Tranebjaerg, Nanna D. Rendtorff, Sascha Vermeer, Jeroen J. Smits, Ronald J. E. Pennings, Marco Aben, Jaap Oostrik, Galuh D. N. Astuti, Jordi Corominas Galbany, Hester Y. Kroes, Milan Phan, Wendy A. G. van Zelst-Stams, Alberta A. H. J. Thiadens, Joke B. G. M. Verheij, Mary J. van Schooneveld, Suzanne E. de Bruijn, Catherina H. Z. Li, Carel B. Hoyng, Christian Gilissen, Lisenka E. L. M. Vissers, Frans P. M. Cremers, Hannie Kremer, Erwin van Wijk, Susanne Roosing
Summary: Whole genome sequencing combined with an improved variant interpretation pipeline was used to assess individuals suspected of having USH2A-associated disease, leading to the identification of causative variants and providing a conclusive genetic diagnosis for rare genetic conditions.
HUMAN GENETICS AND GENOMICS ADVANCES
(2023)
Article
Hematology
Claire C. Homan, Michael W. Drazer, Kai Yu, David M. Lawrence, Jinghua Feng, Luis Arriola-Martinez, Matthew J. Pozsgai, Kelsey E. Mcneely, Thuong Ha, Parvathy Venugopal, Peer Arts, Sarah L. King-Smith, Jesse Cheah, Mark Armstrong, Paul Wang, Csaba Bodor, Alan B. Cantor, Mario Cazzola, Erin Degelman, Courtney D. Dinardo, Nicolas Duployez, Remi Favier, Stefan Froehling, Ana Rio-Machin, Jeffery M. Klco, Alwin Kraemer, Mineo Kurokawa, Joanne Lee, Luca Malcovati, Neil Morgan, Georges Natsoulis, Carolyn Owen, Keyur P. Patel, Claude Preudhomme, Hana Raslova, Hugh Rienhoff, Tim Ripperger, Rachael Schulte, Kiran Tawana, Elvira Velloso, Benedict Yan, Erika Kim, Amy P. NISC Comparative Sequencing Program, Amy P. Hsu, Steven M. Holland, Kerry Phillips, Nicola K. Poplawski, Milena Babic, Andrew H. Wei, Cecily Forsyth, Helen Mar Fan, Ian D. Lewis, Julian Cooney, Rachel Susman, Lucy C. Fox, Piers Blombery, Deepak Singhal, Devendra Hiwase, Belinda Phipson, Andreas W. Schreiber, Christopher N. Hahn, Hamish S. Scott, Paul Liu, Lucy A. Godley, Anna L. Brown
Summary: This study identifies genetic drivers unique to each HER2 syndrome before and after leukemogenesis and may lead to the development of specific clinical trials and gene-specific approaches to clinical monitoring.
Meeting Abstract
Respiratory System
T. Goos, M. Vermant, L. J. De Sadeleer, K. Verstraete, N. De Crem, E. De langhe, A. Dubbeldam, E. K. Verbeken, J. Verschakelen, B. Weynand, J. Yserbyt, S. Vermeer, S. E. Verleden, W. A. Wuyts
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Surgery
Tinne Goos, Stijn E. Verleden, Laurens J. De Sadeleer, Anke Van Herck, Annelore Sacreas, Arno Vanstapel, Janne Kaes, Vincent Geudens, Celine Aelbrecht, David Ruttens, Diether Lambrechts, Sascha Vermeer, Laurens J. Ceulemans, Dirk E. Van Raemdonck, Laurent Godinas, Jonas Yserbyt, Bart M. Vanaudenaerde, Geert M. Verleden, Robin Vos, Wim A. Wuyts
Summary: The MUC5B promoter polymorphism (rs35705950) is associated with high occurrence of ILD and lower occurrence of other chronic respiratory diseases. However, it does not have a significant association with CLAD/graft loss and does not influence the overall outcome of the study cohort.
TRANSPLANT INTERNATIONAL
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jeroen Depreeuw, Barbara Dewaele, Sascha Vermeer, Gert Matthijs, Valerie Race
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)