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)
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)
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)
Article
Neurosciences
Zheng Wang, Callie Lane, Matthew Terza, Pravin Khemani, Su Lui, Walker S. McKinney, Matthew W. Mosconi
Summary: FXTAS is a neurodegenerative disorder associated with a premutation of the FMR1 gene, with gait ataxia and intention tremor as primary behavioral symptoms. This study aimed to clarify the potential of quantitative measures of gait and upper limb kinematics as markers of FXTAS degeneration. Results showed kinematic alterations in individuals with FXTAS, suggesting these measures may serve as critical targets for detecting FXTAS risk and monitoring progression.
Article
Genetics & Heredity
Ramkumar Aishworiya, Dragana Protic, Si Jie Tang, Andrea Schneider, Flora Tassone, Randi Hagerman
Summary: This study identified a high prevalence of fragile X-associated neurodevelopmental disorders (FXAND) in a sample of young individuals with fragile X premutation carrier state (PM). The presence of FXAND and early recognition of associated symptoms may facilitate timely and appropriate care for PM individuals.
Article
Multidisciplinary Sciences
Ramkumar Aishworiya, Ye Hyun Hwang, Ellery Santos, Bruce Hayward, Karen Usdin, Blythe Durbin-Johnson, Randi Hagerman, Flora Tassone
Summary: Carriers of a premutation allele in the FMR1 gene are at risk of developing Fragile X premutation associated disorders. This study aims to examine the clinical association between somatic FMR1 allele instability and PM associated disorders.
SCIENTIFIC REPORTS
(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
Clinical Neurology
Marsha R. Mailick, Jinkuk Hong, Arezoo Movaghar, Leann DaWalt, Elizabeth M. Berry-Kravis, Murray H. Brilliant, Jaime Boero, Peter K. Todd, Deborah Hall
Summary: This study compared unselected carriers of premutation (n = 35, 55-101 CGG repeats) with matched controls (n = 61, 29-39 CGG repeats) for FXTAS-type signs. Results showed a statistically significant age-associated elevation in FXTAS-type signs in premutation carriers compared to controls among individuals without potentially confounding comorbid diagnoses.
MOVEMENT DISORDERS
(2021)
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
Psychiatry
Marwa Zafarullah, Blythe Durbin-Johnson, Emily S. Fourie, David R. Hessl, Susan M. Rivera, Flora Tassone
Summary: FXTAS is a neurodegenerative disorder that affects movement and cognition in carriers of a premutation allele in the FMR1 gene. This study aimed to investigate the correlation between brain changes and metabolic biomarkers in individuals with FXTAS, finding differential metabolite levels between healthy controls and premutation groups. These metabolites suggest potential targets for personalized therapeutic development.
FRONTIERS IN PSYCHIATRY
(2021)
Review
Genetics & Heredity
Nattaporn Tassanakijpanich, Randi J. Hagerman, Juthamas Worachotekamjorn
Summary: FXS is caused by mutations in the FMR1 gene, with carriers possibly exhibiting a premutation. Carriers of the premutation may experience various health issues, including neuropsychiatric disorders and ovarian dysfunction. Physicians need to recognize these problems and provide appropriate management.
Article
Cardiac & Cardiovascular Systems
Noah Gruber, Lilach Marom Haham, Hila Raanani, Yoram Cohen, Lidia Gabis, Michal Berkenstadt, Liat Ries-Levavi, Shai Elizur, Orit Pinhas-Hamiel
Summary: Women with fragile X premutation (FXPC) have an increased metabolic risk, particularly in terms of waist circumference, glucose, and lipid levels. Metabolic screening is recommended for all women with FMR1 premutation to prevent cardiovascular comorbidities.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2022)
Article
Clinical Neurology
Michelle H. S. Tosin, Glenn T. Stebbins, Christopher G. Goetz, Randi J. Hagerman, David Hessl, Melissa A. Zolecki, Peter K. Todd, Maureen A. Leehey, Deborah A. Hall
Summary: This study revised the FXTAS-RS rating scale and successfully established a revised version with 18 items through the Delphi technique and cognitive pretesting. The revised scale is now ready for large-scale field validation.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Jessica Famula, Emilio Ferrer, Randi J. Hagerman, Flora Tassone, Andrea Schneider, Susan M. Rivera, David Hessl
Summary: Carriers of the FMR1 premutation have an increased risk of developing FXTAS, a neurodegenerative disease characterized by intention tremor, ataxia, and cognitive decline. Longitudinal study showed that FMR1 premutation carriers exhibited greater rates of decline in visual working memory, motor dexterity, inhibitory control, and manual movement speed. The findings suggest that executive function decline and subtle motor changes may precede and track with the emergence of FXTAS symptoms.
JOURNAL OF NEURODEVELOPMENTAL DISORDERS
(2022)
Review
Clinical Neurology
Randi Hagerman, Paul Hagerman
Summary: This paper reviews the prevalence, pathophysiology, and management of fragile X-associated tremor/ataxia syndrome (FXTAS). Recent findings suggest that RNA toxicity and altered proteasomal function may play a role in FXTAS pathophysiology. Additionally, FXTAS can co-occur with Parkinson disease and Alzheimer disease, with differing penetrance based on gender and age.
CURRENT OPINION IN NEUROLOGY
(2021)