Article
Biochemistry & Molecular Biology
Georgios Makris, Matthias Lauber, Veronique Ruefenacht, Corinne Gemperle, Carmen Diez-Fernandez, Ljubica Caldovic, D. Sean Froese, Johannes Haeberle
Summary: Genetic analysis, structural considerations, and in vitro experiments suggest that dominant negative effects are unlikely to play a significant role in human proximal urea cycle disorders, as evidenced by the lack of multiprotein complex formation in the urea cycle enzymes studied. Only a small subset of patients with suspected proximal UCDs were identified as having single defective alleles. Potential dominant negative triggers identified in these cases seem to participate in critical intramolecular functions and are unlikely to facilitate protein-protein interactions.
Article
Health Care Sciences & Services
Youn Jung Kim, Yejin Lee, Wonseon Chae, Jung-Wook Kim
Summary: In this study, two families with amelogenesis imperfecta (AI) were recruited and mutational analysis was performed using whole-exome sequencing. Different mutation genes were identified by analyzing the genetic variations of the patients, providing insights into the genetic mechanisms of AI.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Review
Oncology
Dimitrios Vlachakis, Thanasis Mitsis, Nicolas Nicolaides, Aspasia Efthimiadou, Antonis Giannakakis, Flora Bacopoulou, George P. Chrousos
Summary: Studies on extracellular vesicles, particularly exosomes, have shown their multi-dimensional roles in cellular homeostasis, intercellular communication, and disease development. The mechanisms governing these interactions are still not fully understood. The association between endocrine disorders and exosomes highlights their potential as both clinical biomarkers and therapeutic vehicles.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Immunology
Kunihiko Moriya, Tomohiro Nakano, Yoshitaka Honda, Miyuki Tsumura, Masato Ogishi, Motoshi Sonoda, Masahiko Nishitani-Isa, Takashi Uchida, Mohamed Hbibi, Yoko Mizoguchi, Masataka Ishimura, Kazushi Izawa, Takaki Asano, Fumihiko Kakuta, Daiki Abukawa, Darawan Rinchai, Peng Zhang, Naotomo Kambe, Aziz Bousfiha, Takahiro Yasumi, Bertrand Boisson, Anne Puel, Jean-Laurent Casanova, Ryuta Nishikomori, Shouichi Ohga, Satoshi Okada, Yoji Sasahara, Shigeo Kure
Summary: This study reports six patients from five families with RELA mutations, leading to autoinflammatory and autoimmune manifestations. The mutations result in loss of function of RelA protein, leading to excessive IFN expression and autoimmune response. The DN RELA mutations are identified as a novel cause of chronic mucocutaneous ulcerations with autoinflammatory and autoimmune manifestations.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Review
Clinical Neurology
Hayley A. Wilson, Carolyn Creighton, Helen Scharfman, Elena Choleris, Neil J. MacLusky
Summary: Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders that affects males more frequently than females. Genetic and environmental risk factors may contribute to its development, with hormones like gonadal, thyroid, and glucocorticoids potentially playing a role. Environmental factors may influence ASD etiology by affecting neuroendocrine and neuroimmune system development, with the placenta likely serving as a key mediator of these effects on the developing brain, particularly in males. Understanding how various risk factors interact to impact neural development could lead to a better understanding of the causes of ASD.
Article
Agriculture, Dairy & Animal Science
Jiangbo Cheng, Weimin Wang, Deyin Zhang, Yukun Zhang, Xiaolong Li, Yuan Zhao, Dan Xu, Liming Zhao, Wenxin Li, Jianghui Wang, Bubo Zhou, Changchun Lin, Xiaobin Yang, Xiaoxue Zhang
Summary: The aim of this study was to analyze the effect of OSMR and GHR gene polymorphisms on growth traits in sheep. The study found multiple mutation sites in the OSMR and GHR genes, which were significantly correlated with growth traits such as body weight, body length, chest circumference, and cannon circumference in sheep. Furthermore, the study found that sheep with the TTOSMR/AA(GHR) genotype had significantly higher body weight than sheep with other genotypes.
ANIMAL BIOTECHNOLOGY
(2022)
Article
Endocrinology & Metabolism
Afiya Andrews, Emily Cottrell, Avinaash Maharaj, Tasneem Ladha, Jack Williams, Katharina Schilbach, Lena R. Kaisinger, John R. B. Perry, Louise A. Metherell, Peter J. McCormick, Helen L. Storr
Summary: Two novel GHR gene variants were found in two GHI patients, which resulted in increased levels of cleaved GHR and GHBP, leading to inhibition of growth hormone (GH) signaling. These findings suggest a potential therapeutic approach of inhibiting GH binding by excess GHBP.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Nicolas Corniere, R. Brent Thomson, Stephanie Thauvin, Bruno O. Villoutreix, Sophie Karp, Diane W. Dynia, Sarah Burlein, Lennart Brinkmann, Alaa Badreddine, Aurelie Dechaume, Mehdi Derhourhi, Emmanuelle Durand, Emmanuel Vaillant, Philippe Froguel, Regine Chambrey, Peter S. Aronson, Amelie Bonnefond, Dominique Eladari
Summary: Nephrolithiasis is a complex disease affecting a significant portion of the global population, and a rare mutation in the SLC26A6 gene has been identified to be associated with hyperoxaluria, affecting oxalate transport and potentially leading to the formation of calcium oxalate stones.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Gastroenterology & Hepatology
Mukhamad Sunardi, Keisuke Ito, Yuya Sato, Toshihiro Uesaka, Mitsuhiro Iwasaki, Hideki Enomoto
Summary: This study finds that a single RET gene mutation can cause Hirschsprung disease (HSCR) through a dominant-negative mechanism and interacts with other susceptibility genes, providing important insights into the pathogenetic mechanism of HSCR caused by RET mutations.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alex J. McCann, Jieqiong Lou, Mehdi Moustaqil, Matthew S. Graus, Ailisa Blum, Frank Fontaine, Hui Liu, Winnie Luu, Paulina Rudolffi-Soto, Peter Koopman, Emma Sierecki, Yann Gambin, Frederic A. Meunier, Zhe Liu, Elizabeth Hinde, Mathias Francois
Summary: The study reveals that the mutant SOX18(RaOp) disrupts the system through molecular interferences, impairing the functions of wild-type SOX18 protein, and amplifying the dominant-negative effect by poisoning the interactome of its wild-type counterpart.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Clinical Neurology
Gemma L. Carvill, Tyler Matheny, Jay Hesselberth, Scott Demarest
Summary: This review summarizes the pathogenic mechanisms underlying monogenic epilepsies and discusses the potential of novel precision therapeutics in treating these disorders. Understanding the pathogenic mechanisms of each genetic epilepsy is crucial for designing precision therapies that are likely to benefit patients. Novel therapeutics discussed include gene therapy, gene editing, antisense oligonucleotides, and protein replacement, with examples from the literature illustrating and reinforcing the discussions.
Article
Biology
Stephanie R. Sloat, Suzanne Hoppins
Summary: This study investigates a variant of mitofusin found in CMT2A patients, and demonstrates that it blocks mitochondrial fusion. A proposed dynamic model is presented to explain the mechanism behind this variant's effect.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemistry & Molecular Biology
Xianglin Chu, Siyu He, Yang Liu, Yijun Liu, Feng Feng, Qinglong Guo, Li Zhao, Haopeng Sun
Summary: This article provides an overview of the physiological and pathological functions of human aldo-keto reductase family 1C1 (AKR1C1) and its relationship with diseases. It also summarizes the development of AKR1C1 inhibitors and the interaction between inhibitors and AKR1C1. Furthermore, it discusses the design ideals of selective AKR1C1 inhibitors and the prospects of AKR1C1 in disease treatment.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Genetics & Heredity
Ronit Marom, Bo Zhang, Megan E. Washington, I-Wen Song, Lindsay C. Burrage, Vittoria C. Rossi, Ava S. Berrier, Anika Lindsey, Jacob Lesinski, Michael L. Nonet, Jian Chen, Dustin Baldridge, Gary A. Silverman, V. Reid Sutton, Jill A. Rosenfeld, Alyssa A. Tran, M. John Hicks, David R. Murdock, Hongzheng Dai, Maryann Weis, Shalini N. Jhangiani, Donna M. Muzny, Richard A. Gibbs, Richard Caswell, Carrie Pottinger, Deirdre Cilliers, Karen Stals, David Eyre, Deborah Krakow, Tim Schedl, Stephen C. Pak, Brendan H. Lee
Summary: De novo heterozygous variants in KIF5B have been identified in individuals with osteogenesis imperfecta, and these variants are predicted to interfere with nucleotide binding and disrupt cell signaling and function.
Article
Endocrinology & Metabolism
Thierry Brue, Sally A. Camper
Summary: Recent studies have revealed a novel mechanism of combined pituitary hormone deficiency linked to mutations in POU1F1, which alters the balance of alternative splicing and leads to over-expression of the beta isoform of POU1F1. These findings emphasize the importance of investigating alternative splicing in POU1F1 and other genes during routine molecular diagnosis of this condition.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2021)