Article
Clinical Neurology
Maria Jimena Salcedo-Arellano, Jun Yi Wang, Yingratana A. McLennan, Mai Doan, Ana Maria Cabal-Herrera, Sara Jimenez, Marisol W. Wolf-Ochoa, Desiree Sanchez, Pablo Juarez, Flora Tassone, Blythe Durbin-Johnson, Randi J. Hagerman, Veronica Martinez-Cerdeno
Summary: The study aimed to analyze the presence of cerebral microbleeds in patients with fragile X-associated tremor/ataxia syndrome and investigate possible causes for these microbleeds. The results showed an increased number of cerebral microbleeds in the brains of individuals with fragile X-associated tremor/ataxia syndrome, indicating cerebrovascular dysfunction. Additionally, a suggestive association between the presence of amyloid beta in capillaries and disease progression rate was found.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Brett D. Dufour, Sarwat Amina, Veronica Martinez-Cerdeno
Summary: The study found significant increases in the pro-inflammatory cytokines TNF alpha and IL-12 in the brains of FXTAS patients, which are implicated in the pathogenesis of other neurodegenerative disorders such as Multiple Sclerosis.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Multidisciplinary Sciences
Yogeeshwar Ajjugal, Narendar Kolimi, Thenmalarchelvi Rathinavelan
Summary: CGG tandem repeat expansion in the FMR1 gene leads to unusual nucleic acid conformations, causing genetic instabilities. The number of G...G or C...C mismatches dictates the secondary structural choice of the FMR1 gene and its transcripts, affecting RNA structure in FXTAS.
SCIENTIFIC REPORTS
(2021)
Article
Geriatrics & Gerontology
Juan Chen, Yuwen Zhao, Xun Zhou, Jin Xue, Qiao Xiao, Hongxu Pan, Xiaoxia Zhou, Yaqin Xiang, Jian Li, Liping Zhu, Zhou Zhou, Yang Yang, Qian Xu, Qiying Sun, Xinxiang Yan, Jieqiong Tan, Jinchen Li, Jifeng Guo, Ranhui Duan, Beisha Tang, Qiao Yu, Zhenhua Liu
Summary: This study found that the GZ allele of FMR1 CGG repeat expansions was not significantly enriched in Chinese PD patients, suggesting that it may not be strongly associated with PD in this population. However, two PD patients were found to have FMR1 premutation.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Neurosciences
Maria Jimena Salcedo-Arellano, Desiree Sanchez, Jun Yi Wang, Yingratana A. McLennan, Courtney Jessica Clark, Pablo Juarez, Andrea Schneider, Flora Tassone, Randi J. Hagerman, Veronica Martinez-Cerdeno
Summary: This case report documents the co-occurrence of FXTAS and AD in a 71-year-old carrier with rapid cognitive decline and remarkable MRI changes.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cell Biology
Jun Yi Wang, Gerard J. Sonico, Maria Jimena Salcedo-Arellano, Randi J. Hagerman, Veronica Martinez-Cerdeno
Summary: We conducted a postmortem MRI study of FXTAS to investigate cerebrovascular disease, brain atrophy, and iron content, and found that both ischemic and hemorrhagic brain damage may occur in FXTAS, with different characteristics. The former is marked by demyelination/iron depletion and atrophy, while the latter is characterized by intracranial hemorrhage (ICH) and iron accumulation in basal ganglia.
Article
Medicine, General & Internal
Maria Isabel Alvarez-Mora, Ines Agusti, Robin Wijngaard, Estefania Martinez-Barrios, Tamara Barcos, Aina Borras, Sara Peralta, Marta Guimera, Ana Goday, Dolors Manau, Laia Rodriguez-Revenga
Summary: The study found a significant association between FXPOI and high expression levels of FMR4 in female FMR1 premutation carriers, suggesting a potential role of FMR4 as a biomarker for FXPOI.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
Milica Pesic, Natasa Dragasevic Miskovic, Ana Marjanovic, Valerija Dobricic, Nela Maksimovic, Marina Svetel, Dijana Perovic, Ivana Novakovic, Sanja Cirkovic, Iva Stankovic, Vladimir Kostic
Summary: This study estimated the frequency of premutation carriers in patients with unexplained degenerative ataxias, action tremor or parkinsonism, and found a rate of 2%. While FXTAS was relatively rare in these patients, it should still be considered in the differential diagnosis for those with unexplained action tremor and ataxia.
NEUROLOGICAL RESEARCH
(2021)
Article
Pathology
Elizabeth Berry-Kravis, Lili Zhou, Jonathan Jackson, Flora Tassone
Summary: The novel CGG repeat primed FMR1 PCR assay designed in 2009 allows consistent detection of large full mutation alleles, resolution of heterozygosity in females, and mapping of AGG interspersions. The AmplideX Fragile X Dx and Carrier Screen Kit has been validated for FDA approval, showing high accuracy and efficiency in determining FMR1 allele size. This assay is considered a highly accurate and time-efficient method for FMR1 allele size determination, with limitations including no methylation assessment and difficulty in detecting full mutation peaks in some mosaic samples.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(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
Medical Laboratory Technology
Qiaowei Liang, Yingdi Liu, Yaning Liu, Ranhui Duan, Wanli Meng, Jiahan Zhan, Jiahui Xia, Aiping Mao, Desheng Liang, Lingqian Wu
Summary: This study developed a new genetic testing method, comprehensive analysis of FXS (CAFXS), which utilizes long-range PCR and long-read sequencing to accurately detect FMR1 CGG expansions and identify AGG interruptions, rare intragenic variants, and large gene deletions. CAFXS greatly improves the accuracy of genetic screening and diagnosis for fragile X syndrome.
CLINICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Helene Tran, Michael P. Moazami, Huiya Yang, Diane McKenna-Yasek, Catherine L. Douthwright, Courtney Pinto, Jake Metterville, Minwook Shin, Nitasha Sanil, Craig Dooley, Ajit Puri, Alexandra Weiss, Nicholas Wightman, Heather Gray-Edwards, Miklos Marosfoi, Robert M. King, Thomas Kenderdine, Daniele Fabris, Robert Bowser, Jonathan K. Watts, Robert H. Brown
Summary: The study successfully generated and optimized ASOs that blunt the G(4)C(2) repeat-containing transcripts in the C9ORF72 gene, demonstrating potential therapeutic efficacy for patients with ALS and FTD.
Article
Biochemistry & Molecular Biology
Danuta Z. Loesch, Flora Tassone, Anna Atkinson, Paige Stimpson, Nicholas Trost, Dean L. Pountney, Elsdon Storey
Summary: Expansions of the CGG repeat in the non-coding segment of the FMR1 X-linked gene are associated with various phenotypic changes. Female carriers of the fragile X premutation may themselves experience a wide range of clinical problems, with the most severe being Fragile X-Associated Tremor Ataxia Syndrome (FXTAS). Male premutation carriers have a higher risk of developing FXTAS, but sex-specific differences in clinical manifestations and progression are poorly documented.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Medicine, Research & Experimental
Indranil Malik, Yi-Ju Tseng, Shannon E. Wright, Kristina Zheng, Prithika Ramaiyer, Katelyn M. Green, Peter K. Todd
Summary: The study shows that CGG repeat RNA binding proteins play crucial roles in RAN translation and repeat toxicity, and inhibiting SRPK can alleviate toxicity in fruit flies and rodent neuron models.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Sarah L. Nolin, Eleonora Napoli, Amanda Flores, Randi J. Hagerman, Cecilia Giulivi
Summary: Metabolomics and proteomics analysis on amniotic fluid revealed mitochondrial deficits in pregnant women carrying fragile X syndrome, with noted defects in serine biosynthesis at the Krebs cycle level. Restoring mitochondrial function was achieved by using alpha-ketoglutarate precursors, suggesting potential benefits of maternal administration of serine and its precursors in reducing the risk of energy shortages associated with mitochondrial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)