Article
Medicine, Research & Experimental
Karima Habbas, Oktay Cakil, Boglarka Zambo, Ricardos Tabet, Fabrice Riet, Doulaye Dembele, Jean-Louis Mandel, Michael Hocquemiller, Ralph Laufer, Francoise Piguet, Herve Moine
Summary: Fragile X syndrome (FXS) is a common form of familial intellectual disability caused by the lack of RNA-binding protein FMRP. This study demonstrates that DGKk, an mRNA target of FMRP and a regulator of lipid signaling, plays an important role in FXS pathogenesis, and the delivery of modified and FMRP-independent DGKk can correct abnormal lipid signaling and behavioral phenotypes in FXS mice.
EMBO MOLECULAR MEDICINE
(2022)
Article
Medical Laboratory Technology
Fei Hou, Aiping Mao, Shan Shan, Yan Li, Wanli Meng, Jiahan Zhan, Wenying Nie, Hua Jin
Summary: This study evaluated the clinical utility of a long-read sequencing-based assay called comprehensive analysis of FXS (CAFXS) in high-risk samples and compared it to conventional PCR assays. The results showed that CAFXS could detect FXS genetic variations more comprehensively and accurately, providing more information for genetic counseling.
CLINICA CHIMICA ACTA
(2023)
Article
Neurosciences
Nicole K. Morrill, Aurelie Joly-Amado, Qingyou Li, Sahana Prabhudeva, Edwin J. Weeber, Kevin R. Nash
Summary: This study found that the reduction in Reelin may be related to FXS, and enhancing the Reelin signaling successfully rescued cognitive deficits in FXS mice, providing a feasible therapeutic approach.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Ha Eun Kong, Junghwa Lim, Alexander Linsalata, Yunhee Kang, Indranil Malik, Emily G. Allen, Yiqu Cao, Lisa Shubeck, Rich Johnston, Yanting Huang, Yanghong Gu, Xiangxue Guo, Michael E. Zwick, Zhaohui Qin, Thomas S. Wingo, Jorge Juncos, David L. Nelson, Michael P. Epstein, David J. Cutler, Peter K. Todd, Stephanie L. Sherman, Stephen T. Warren, Peng Jin
Summary: This study identified Prosbeta5 (PSMB5) as a candidate genetic modifier for FXTAS using a Drosophila model. Knockdown of PSMB5 suppressed CGG-associated neurodegeneration in flies and cells. Additionally, an expression quantitative trait locus variant in PSMB5 was associated with delayed onset of FXTAS in human carriers. These findings suggest a therapeutic strategy for FXTAS by targeting PSMB5.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Se Jin Jeon, Huiyoung Kwon, Ho Jung Bae, Edson Luck Gonzales, Junhyeong Kim, Hye Jin Chung, Dong Hyun Kim, Jong Hoon Ryu, Chan Young Shin
Summary: This study found that agmatine can reverse FXS symptoms in Fmr1 KO mouse model, including compulsions, learning and memory deficits, hyperactivity, aberrant social interaction, and communication deficit, while normalizing abnormal long-term potentiation and depression in the hippocampus.
Review
Genetics & Heredity
Aadil Yousuf, Nadeem Ahmed, Abrar Qurashi
Summary: Fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X syndrome (FXS) are distinct disorders caused by abnormal expansion of CGG repeats. FXTAS is a neurodegenerative disorder characterized by gene hyperexpression, while FXS is a neurodevelopmental disorder characterized by gene silencing. Non-canonical DNA and RNA structures formed from CGG repeat expansions can disrupt cellular processes and have different effects in these two disorders.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Dragana D. Protic, Ramkumar Aishworiya, Maria Jimena Salcedo-Arellano, Si Jie Tang, Jelena Milisavljevic, Filip Mitrovic, Randi J. Hagerman, Dejan B. Budimirovic
Summary: FXS is a neurodevelopmental disorder that can be improved through early diagnosis and interventions targeting behavior symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Genetics & Heredity
Maria Jose Gomez-Rodriguez, Montserrat Morales-Conejo, Ana Arteche-Lopez, Maria Teresa Sanchez-Calvin, Juan Francisco Quesada-Espinosa, Irene Gomez-Manjon, Carmen Palma-Milla, Jose Miguel Lezana-Rosales, Ruben Perez de la Fuente, Maria-Luisa Martin-Ramos, Manuela Fernandez-Guijarro, Marta Moreno-Garcia, Maria Isabel Alvarez-Mora
Summary: This manuscript reports a case of FXS caused by an entire hemizygous deletion of the FMR1 gene caused by maternal mosaicism, and reviews the clinical manifestations presented by carriers of FMR1 gene deletions in mosaicism.
Review
Biochemistry & Molecular Biology
Merlin G. Butler, Waheeda A. Hossain, Jacob Steinle, Harry Gao, Eleina Cox, Yuxin Niu, May Quach, Olivia J. Veatch
Summary: Fragile X syndrome is a common inherited cause of intellectual disabilities, and recent studies have found an association between intermediate or gray zone alleles and connective tissue involvement in females.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Rob Willemsen, R. Frank Kooy
Summary: Fragile X-related disorders are caused by expanded CGG repeats in the FMR1 gene and can manifest as either neurodegenerative or neurodevelopmental disorders. Mouse models have provided valuable insights into these disorders and their translational value for developing targeted therapies for intellectual disability and autism disorders.
DISEASE MODELS & MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Pamela R. Westmark, Aaron K. Gholston, Timothy J. Swietlik, Rama K. Maganti, Cara J. Westmark
Summary: This study assessed sleep-wake cycles in mice with different genotypes and dietary interventions. The results showed that a high-fat, low-carbohydrate ketogenic diet increased non-rapid eye movement (NREM) sleep and decreased activity levels in both wild type and Fmr1(KO) mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Pedro A. A. Villa, Nancy M. M. Lainez, Carrie R. R. Jonak, Sarah C. C. Berlin, Iryna M. M. Ethell, Djurdjica Coss
Summary: Mutations in the FMR1 gene are associated with Fragile X Syndrome and reproductive disorders. This study demonstrates that female mice with Fmr1 null mutations stop reproducing early but have larger litters and increased hormone levels. The dysregulation of synaptic molecules in the hypothalamus and alterations in ovarian function contribute to these reproductive disorders. The results suggest that Fmr1 plays a role in the regulation of GnRH neuron secretion and highlights the importance of GnRH neurons in the etiology of Fmr1-mediated reproductive disorders.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Poonnada Jiraanont, Esther Manor, Nazi Tabatadze, Marwa Zafarullah, Guadalupe Mendoza, Gia Melikishvili, Flora Tassone
Summary: Fragile X syndrome is the most common cause of X-linked inherited intellectual disabilities and the most frequent monogenic form of autism spectrum disorders. It is caused by CGG trinucleotide repeat expansion in the FMR1 gene, leading to the absence of the fragile X mental retardation protein, FMRP. Other mechanisms such as deletions or point mutations of the FMR1 gene can also cause fragile X syndrome.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Erdi Kucuk, Bart P. G. H. van der Sanden, Luke O'Gorman, Michael Kwint, Ronny Derks, Aaron M. Wenger, Christine Lambert, Shreyasee Chakraborty, Primo Baybayan, William J. Rowell, Han G. Brunner, Lisenka E. L. M. Vissers, Alexander Hoischen, Christian Gilissen
Summary: Long-read sequencing techniques have been successful in identifying structural variants. However, the high error rate of these techniques makes detecting small variants challenging. The introduction of PacBio HiFi sequencing allows for the detection of small variations. This study evaluates the ability of HiFi sequencing to detect de novo mutations of all types.
Article
Psychiatry
Heather Fielding-Gebhardt, Rebecca Swinburne Romine, Shelley Bredin-Oja, Nancy Brady, Steven F. Warren
Summary: Mothers of children with fragile X syndrome are more likely to experience anxiety and depression due to genetic risk and parenting stress. During the COVID-19 pandemic, their levels of anxiety and depression were elevated. The impacts of the pandemic and related stressors on their families directly affected their mental well-being.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Genetics & Heredity
Mengmeng Liu, Yunshan Zhong, Hongqian Liu, Desheng Liang, Erhong Liu, Yu Zhang, Feng Tian, Qiaowei Liang, David S. Cram, Hua Wang, Lingqian Wu, Fuli Yu
MOLECULAR GENETICS & GENOMIC MEDICINE
(2020)
Article
Pathology
Qiaowei Liang, Wanqian Gu, Ping Chen, Yuezhen Li, Yanqiu Liu, Mao Tian, Qiaomiao Zhou, Hongbo Qi, Yuhong Zhang, Jun He, Qing Li, Lingfang Tang, Juan Tang, Yanling Teng, Yulin Zhou, Shengwen Huang, Zongjie Lu, Mengnan Xu, Wei Hou, Ting Huang, Youqiong Li, Rong Li, Lanping Hu, Shaoying Li, Qiwei Guo, Zhaozhen Zhuo, Yan Mou, David S. Cram, Lingqian Wu
Summary: The study evaluated the clinical utility of a third-generation sequencing approach, CATSA, for diagnosing thalassemia genetic carriers. CATSA effectively identified pathogenic thalassemia variants, including rare ones, improving diagnostic accuracy for carriers.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2021)