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
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
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)
Article
Clinical Neurology
Erin E. Robertson-Dick, Emily C. Timm, Gian Pal, Bichun Ouyang, Yuanqing Liu, Elizabeth Berry-Kravis, Deborah A. Hall, Joan A. O'Keefe
Summary: This is the first quantitative study demonstrating distinct gait and functional mobility profiles in FXTAS, PD, and ET which may assist in more accurate and timely diagnosis.
FRONTIERS IN NEUROLOGY
(2023)
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)
Article
Neurosciences
Arun Kumar Verma, Eshan Khan, Subodh Kumar Mishra, Amit Kumar
Summary: By screening a small molecule library, we have identified three candidate molecules with high affinity and selectivity that can improve the pathological effects of CGG repeat RNA and reduce protein aggregation, suggesting their potential as lead molecules for therapeutics against FXTAS.
MOLECULAR NEUROBIOLOGY
(2022)
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
Clinical Neurology
Ryo Oike, Yasuaki Inoue, Jun Mitsui, Yoshiaki Ota
Summary: Clinical management of patients with fragile X-associated tremor/ataxia syndrome (FXTAS) is challenging and there is no established treatment. Diagnosis of coexistent idiopathic normal pressure hydrocephalus (iNPH) with FXTAS is also difficult. We present a case of a genetically diagnosed FXTAS patient who was successfully treated with shunt surgery and subsequently diagnosed with iNPH, suggesting the management of coexistent iNPH with FXTAS when clinically suspected.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2022)
Article
Multidisciplinary Sciences
Hideo Shimizu, Hirohiko Hohjoh
Summary: This study reveals that FMR1, FXR1, and Dlg4 genes associated with Fragile X syndrome are involved in the regulation of UPS activity and affect neurite outgrowth.
SCIENTIFIC REPORTS
(2023)
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)
Article
Biochemistry & Molecular Biology
Marwa Zafarullah, Jie Li, Michelle R. Salemi, Brett S. Phinney, Blythe P. Durbin-Johnson, Randi Hagerman, David Hessl, Susan M. Rivera, Flora Tassone
Summary: FXTAS is a neurodegenerative disorder associated with the FMR1 premutation. By analyzing the proteome of premutation carriers, researchers have identified differentially expressed proteins and dysregulated metabolic pathways associated with FXTAS. This provides clues for early diagnosis, development, and progression of FXTAS, as well as the study of related pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Emily Graves Allen, Krista Charen, Heather S. Hipp, Lisa Shubeck, Ashima Amin, Weiya He, Sarah L. Nolin, Anne Glicksman, Nicole Tortora, Bonnie McKinnon, Katharine E. Shelly, Stephanie L. Sherman
Summary: The study revealed that women with 70-100 CGG repeats are at the highest risk for FXPOI, with those having 85-89 repeats having the highest risk; notably, women with 120 repeats did not show a significantly increased risk for FXPOI compared to those with <45 repeats.
GENETICS IN MEDICINE
(2021)
Review
Medicine, General & Internal
Daniele Orsucci, Lucia Lorenzetti, Fulvia Baldinotti, Andrea Rossi, Edoardo Vitolo, Fabio Luigi Gheri, Alessandro Napolitano, Giancarlo Tintori, Marco Vista
Summary: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a premutation in the FMR1 gene. In females, FXTAS has a broad spectrum of symptoms ranging from relatively severe cases starting in mid-adulthood to mild cases beginning in later life.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Neurosciences
Steven Colvin, Nick Lea, Qiangge Zhang, Martin Wienisch, Tobias Kaiser, Tomomi Aida, Guoping Feng
Summary: This study suggests that the length of CGG repeat in mouse models is unlikely to be the main factor preventing methylation and alternative models closer to humans may be required to effectively study FXS.
