Article
Pediatrics
Osama Y. Muthaffar, Angham Abdulrhman Abdulkareem, Abrar Ashi, Muhammad Imran Naseer
Summary: This study identified a novel variant in the LRPPRC gene in a family with Leigh syndrome-like phenotype. Whole exome sequencing and Sanger sequencing confirmed the pathogenicity of this variant. The findings suggest that WES can be used as a first-line diagnostic tool for familial cases and help resolve unresolved molecular diagnoses.
FRONTIERS IN PEDIATRICS
(2023)
Article
Genetics & Heredity
Tania Cruz Marino, Jessica Tardif, Josianne Leblanc, Janie Lavoie, Pascal Morin, Michel Harvey, Marie-Jacqueline Thomas, Annabelle Pratte, Nancy Braverman
Summary: The French-Canadian population in Saguenay-Lac-Saint-Jean is known for its homogenous genetic background, and the hereditary causes of hearing loss have not been explored in this population before. Through a regional clinical evaluation strategy and a comprehensive multigene panel approach, 16 causal variants for hearing loss were identified, with 8 of them being previously unreported.
Article
Cell Biology
Jiaqi Zou, Xiaotong Wu, Chenggang Shi, Yanhong Zhong, Lei Zhang, Qiuning Yan, Liuru Su, Guang Li
Summary: Amphioxus is a promising model organism for understanding the origin and evolution of vertebrates. The study found a correlation between mutation efficacy and type in the tail tips and gametes of amphioxus founders injected with Cas9 protein and sgRNAs. Additionally, a positive relationship was observed between gene insertions in the tail tips and gametes of amphioxus founders injected with Tol2 transposase and transgenic constructs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Genetics & Heredity
Mbarka Bchetnia, Jessica Tardif, Charles Morin, Catherine Laprise
Summary: By analyzing the transcriptomes of LSFC cell lines and healthy cell lines, this study identified altered biological pathways in Leigh syndrome, French-Canadian type (LSFC) and found that genes involved in the mitochondrial respiratory chain and energy production were the most important potential factors in this disease.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2022)
Article
Genetics & Heredity
Qingming Wang, Ye Han, Xinlong Zhou, ShuangXi Cheng, Xin Wang, Xiaoli Chen, Haiming Yuan
Summary: This article reports three Chinese patients with Aicardi-Goutieres syndrome 3 caused by pathogenic variants in the RNASEH2C gene. The patients exhibited new clinical features, including mouth ulcers, hip dysplasia, delayed dentition, and hypogonadism.
Article
Endocrinology & Metabolism
Aaron Chapla, Jabasteen Johnson, Sophy Korula, Nisha Mohan, Anish Ahmed, Deny Varghese, Parthiban Rangasamy, Lavanya Ravichandran, Felix Jebasingh, Krishna Kumar Agrawal, Noel Somasundaram, Asha Hesarghatta Shyamasunder, Sarah Mathai, Anna Simon, Sujeet Jha, Subhankar Chowdry, Radha Venkatesan, Palany Raghupathy, Nihal Thomas
Summary: This study identified 11 patients with WFS1 gene variants through next-generation sequencing. It found that 9 of these patients had pathogenic/likely pathogenic variants in the WFS1 gene, and 3 of them carried a novel variant. Haplotype analysis suggested a founder effect in 3 families from Southern India.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Pediatrics
Jian-Min Liang, Cui-Juan Xin, Guang-Liang Wang, Xue-Mei Wu
Summary: Multiple causative mutations in mitochondrial and nuclear DNA have been identified in Leigh syndrome patients, including a novel mutation m.13513 G>A reported for the first time in a Chinese patient. A case of a Chinese boy diagnosed with Leigh syndrome and WPW syndrome was described, highlighting the geographical and racial variability of the disease.
FRONTIERS IN PEDIATRICS
(2021)
Article
Medicine, General & Internal
Jian-Min Liang, Cui-Juan Xin, Guang-Liang Wang, Xue-Mei Wu
Summary: Leigh syndrome, a mitochondrial disease, can present in both early-onset and late-onset forms with significant phenotypic variability. This case describes a 12-year-old boy with an unusual late-onset, fulminant form of maternally inherited LS without developmental delay, who died within 2 months of hospital admission.
WORLD JOURNAL OF CLINICAL CASES
(2021)
Article
Cardiac & Cardiovascular Systems
Ewa Sieliwonczyk, Maaike Alaerts, Tomas Robyns, Dorien Schepers, Charlotte Claes, Anniek Corveleyn, Rik Willems, Emeline M. Van Craenenbroeck, Eline Simons, Aleksandra Nijak, Bert Vandendriessche, Geert Mortier, Christiaan Vrints, Pieter Koopman, Hein Heidbuchel, Lut Van Laer, Johan Saenen, Bart Loeys
Summary: The study identified the first Belgian SCN5A founder mutation, c.4813 + 3_4813 + 6dupGGGT, and explored its clinical impact on carriers. The majority of mutation carriers showed cardiac electrical abnormalities, with conduction defects being the most common. The high phenotypic heterogeneity and variable penetrance in these families suggest the influence of other genetic and environmental factors on disease severity and outcome.
Article
Clinical Neurology
Ji-Hoon Na, Young -Mock Lee
Summary: This study investigated the distribution of mutant loads of different mtDNA mutations in patients with Leigh syndrome and found that MT-ATP6 had significantly higher mutant load compared with MT-ND3 and MT-ND5. The mutation loads varied significantly among patients carrying the MT-ATP6, MT-ND3, and MT-ND5 mutations.
PEDIATRIC NEUROLOGY
(2023)
Article
Endocrinology & Metabolism
Tania Cruz Marino, Helene Villeneuve, Josianne Leblanc, Caroline Duranceau, Philippe Caron, Charles Morin, Marcel Milot, Raphaelle Chretien, Maude-Marie Gagnon, Jean Mathieu, Benjamin Ellezam, Daniela Buhas
Summary: This study investigated the phenotype and genotype of French-Canadian patients with APECED, revealing a new founder population in the Saguenay-Lac-Saint-Jean region. Muscle biopsy findings expanded the understanding of APECED-related myopathology. The c.1616C > T variant in the AIRE gene was found to be responsible for 100% of APECED cases in the French-Canadian population.
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
Multidisciplinary Sciences
Marie-Eve Lavoie, Jolyane Meloche, Anne-Marie Boucher-Lafleur, Paul Begin, Charles Morin, Louis-Philippe Boulet, Anne-Marie Madore, Catherine Laprise
Summary: This study is a follow-up of 125 participants from the Saguenay-Lac-Saint-Jean asthma family cohort in Canada over a period of 10-20 years. The study aims to explore the appearance, persistence, and progression of asthma. The results show that 12% of participants without asthma at recruitment developed adult-onset asthma, and 7% of individuals with asthma developed chronic obstructive pulmonary disease. Lung function decreased in all groups.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Ke Gong, Li Xie, Zhong-shi Wu, Xia Xie, Xing-xing Zhang, Jin-Lan Chen
Summary: This case study highlights the importance of gene detection in improving diagnostic accuracy, especially in developing countries like China. By identifying a PDHA1 mutation as the underlying cause of Leigh syndrome in a 12-year-old boy, and predicting changes in protein structure, the study provides valuable insights into the treatment of this genetic disorder. The patient's condition significantly improved after receiving targeted therapy.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Despina Hadjipanagi, Gregory Papagregoriou, Constantina Koutsofti, Christiana Polydorou, Polichronis Alivanis, Aimilios Andrikos, Stalo Christodoulidou, Manthos Dardamanis, Athanasios A. Diamantopoulos, Anastasios Fountoglou, Eleni Frangou, Eleni Georgaki, Ioannis Giannikouris, Velissarios Gkinis, Pavlos C. Goudas, Rigas G. Kalaitzidis, Nikolaos Kaperonis, Georgios Koutroumpas, George Makrydimas, Grigorios Myserlis, Andromachi Mitsioni, Christos Paliouras, Fotios Papachristou, Dorothea Papadopoulou, Nikolaos Papagalanis, Aikaterini Papagianni, Garyfalia Perysinaki, Ekaterini Siomou, Konstantinos Sombolos, Ioannis Tzanakis, Georgios V. Vergoulas, Nicoletta Printza, Constantinos Deltas
Summary: Alport syndrome is the most frequent monogenic inherited glomerulopathy with genetic and clinical heterogeneity. Timely genetic diagnosis is important to avoid unnecessary diagnostic investigations and medications, delay kidney failure, and improve treatment outcomes.
Article
Cell Biology
Alexandre Bergeron, Andra Brezai, Rami Shukr, Louis Villeneuve, Bruce G. Allen, Wasay M. S. Qureshi, Kathryn E. Hentges, Angelino Calderone
Summary: The study found that the appearance of nestin in neonatal rat ventricular cardiomyocytes was associated with a migratory phenotype, and the cotreatment with p38 mitogen-activated protein kinase inhibitor promoted the synthesis of nestin. Additionally, the reorganization of nonmuscle myosin IIB and its physical interaction with nestin may act together to facilitate the migratory phenotype in cardiomyocytes.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Doa'a G. F. Al-U'datt, Bruce G. Allen, Roddy Hiram, Nasr Alrabadi
Summary: Peptidylarginine deiminase (PAD) family members play a critical role in maintaining ECM stability during remodelling in various heart diseases, yet the specific mechanisms and therapeutic properties have not been fully explored.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Emile Belanger, Anne-Marie Madore, Anne-Marie Boucher-Lafleur, Marie-Michelle Simon, Tony Kwan, Tomi Pastinen, Catherine Laprise
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cardiac & Cardiovascular Systems
Matthieu Ruiz, Maya Khairallah, Dharmendra Dingar, George Vaniotis, Ramzi J. Khairallah, Benjamin Lauzier, Simon Thibault, Joelle Trepanier, Yanfen Shi, Annie Douillette, Bahira Hussein, Sherin Ali Nawaito, Pramod Sahadevan, Albert Nguyen, Fatiha Sahmi, Marc-Antoine Gillis, Martin G. Sirois, Matthias Gaestel, William C. Stanley, Celine Fiset, Jean-Claude Tardif, Bruce G. Allen
Summary: The study showed that MK2(-/-) mice exhibited signs of possible early diastolic dysfunction at 12 weeks of age; they also had lower body temperature, decreased body weight, and altered expression of certain metabolic genes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Biochemical Research Methods
Pramod Sahadevan, Bruce G. Allen
Summary: Cardiac fibroblasts play a critical role in maintaining the extracellular matrix, wound healing, and cardiac interstitial fibrosis. A method for isolating and maintaining these fibroblasts in vitro allows for a better understanding of their biology and response to fibrotic stimuli.
Article
Gastroenterology & Hepatology
Gabrielle Boucher, Alexandre Paradis, Genevieve Chabot-Roy, Lise Coderre, Erin E. Hillhouse, Alain Bitton, Christine Des Rosiers, Megan K. Levings, L. Philip Schumm, Mark Lazarev, Steve R. Brant, Richard Duerr, Dermot McGovern, Mark S. Silverberg, Judy Cho, Sylvie Lesage, John D. Rioux
Summary: This study identified elevated levels of multiple serum analytes in Crohn's disease (CD) patients, implicating multiple cell types from the immune, epithelial, and endothelial systems. These circulating analytes reflect the ongoing inflammatory processes within the gut. Furthermore, distinct profiles according to disease location support the biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.
INFLAMMATORY BOWEL DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Emile Belanger, Catherine Laprise
Summary: Epigenetics is a study of changes in gene expression influenced by environment or social factors, involving mechanisms such as DNA methylation, histone modification, and noncoding RNA. Understanding epigenetic mechanisms in human diseases provides valuable insights into disease severity and development. Research on the regulation of allergies and asthma through epigenetic mechanisms, particularly using eosinophil samples, is limited, but can enhance understanding of eosinophil recruitment in allergic and asthmatic symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Hassan Nassour, Tuan Anh Hoang, Ryan D. Martin, Juliana C. C. Dallagnol, Etienne Billard, Myriam Letourneau, Ettore Novellino, Alfonso Carotenuto, Bruce G. Allen, Jason C. Tanny, Alain Fournier, Terence E. Hebert, David Chatenet
Summary: The urotensinergic system, consisting of one G protein-coupled receptor and two endogenous ligands, has shown potential as a new target for cardiovascular disease treatment but faces challenges in the development of therapeutic drugs. Pepducins derived from the human urotensin II receptor could be unique tools for studying hUT signaling networks.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Lise Coderre, Lyna Debieche, Joelle Plourde, Remi Rabasa-Lhoret, Sylvie Lesage
Summary: Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in cystic fibrosis patients, with a prevalence of over 50% in adults. The etiology of CFRD is not fully understood, but research suggests it may result from beta-cell extrinsic factors. Inflammation and ductal cells near beta-cells could play a role in CFRD development.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Hematology
Imane Boukhatem, Samuel Fleury, Melanie Welman, Jessica Le Blanc, Chantal Thys, Kathleen Freson, Myron G. Best, Thomas Wurdinger, Bruce G. Allen, Marie Lordkipanidze
Summary: Research has shown that circulating BDNF levels appear to regulate platelet activation, aggregation, and secretion through activation of a truncated TrkB receptor and downstream kinase-dependent signaling. BDNF not only plays a role in neurons but also has important functions in platelets.
Article
Biology
Alexanne Cuillerier, Matthieu Ruiz, Caroline Daneault, Anik Forest, Jenna Rossi, Goutham Vasam, George Cairns, Virgilio Cadete, Christine Des Rosiers, Yan Burelle
Summary: This study investigates compensatory mechanisms in mice with liver-specific knockout of LRPPRC, revealing a network of molecular adjustments, including mitochondrial biogenesis, mitoribosome upregulation, and supercomplex assembly, to maintain mitochondrial integrity and function in the face of OXPHOS defects. Despite a severe reduction in ETC complex IV activity, these mice show no signs of liver failure, suggesting the presence of proteostatic mechanisms and supercomplex stabilization as key factors in preserving ETC function under low LRPPRC levels.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Gerald Coulis, Avinash D. Londhe, R. Sudheer Sagabala, Yanfen Shi, David P. Labbe, Alexandre Bergeron, Pramod Sahadevan, Sherin A. Nawaito, Fatiha Sahmi, Marie Josse, Valerie Vinette, Marie-Claude Guertin, Gerard Karsenty, Michel L. Tremblay, Jean-Claude Tardif, Bruce G. Allen, Benoit Boivin
Summary: Increased production of reactive oxygen species is essential in the pathogenesis of several diseases, including cardiac hypertrophy. The reversible oxidation and inactivation of protein tyrosine phosphatase 1B (PTP1B), along with its substrate argonaute 2 (AGO2), play crucial roles in cardiac hypertrophy.
Review
Cell Biology
Grace R. Mazarura, Juliana C. C. Dallagnol, David Chatenet, Bruce G. Allen, Terence E. Hebert
Summary: The role of G protein-coupled receptors (GPCRs) in the cardiovascular system has been well studied in cardiomyocytes and vascular smooth muscle cells (VSMCs). This article focuses on the relatively less understood effects of GPCRs in cardiac fibroblasts, examining the key signaling events and cellular communications involved in their activation and differentiation. The study highlights the importance of the localization of GPCRs and their associated signaling machinery in these cells, particularly the nuclear membrane-localized receptors, in cardiac fibrosis.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biology
Jana Schuettpelz, Alexandre Janer, Hana Antonicka, Eric A. Shoubridge
Summary: Mutations in SLC25A46 gene are associated with various neurodegenerative diseases affecting mitochondrial morphology. Using a knock-out cell line, we investigated the pathogenicity of three variants and found that they led to fragmented or hyperfused mitochondria. SLC25A46 localized at mitochondrial branch points and tips of tubules and played a role in fission/fusion events. Loss of SLC25A46 function altered the oligomerization state of OPA1 and MFN2 and affected mitochondrial lipid composition.
LIFE SCIENCE ALLIANCE
(2023)
Article
Microbiology
William Bourumeau, Karine Tremblay, Guillaume Jourdan, Catherine Girard, Catherine Laprise
Summary: This study finds that COVID-19 infection leads to dysbiosis in the upper respiratory tract, and identifies different biomarkers for positive and negative-tested individuals. These findings suggest that individuals with prior dysbiosis may have a higher risk of opportunistic pathogen infections.