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
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
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.
Review
Clinical Neurology
Ramkumar Aishworiya, Dragana Protic, Randi Hagerman
Summary: There is increasing recognition of the heterogeneity of origin of cases of autism spectrum disorder (ASD), with genetic etiology identified in 20-40% of cases. The Fragile X premutation state is a newly discovered disease state associated with various disorders, including ASD, and understanding molecular mechanisms may facilitate targeted treatments in the future.
JOURNAL OF NEUROLOGY
(2022)
Review
Psychiatry
Andrea Elias-Mas, Maria Isabel Alvarez-Mora, Conxita Caro-Benito, Laia Rodriguez-Revenga
Summary: FMR1 premutation carriers are at risk of developing neurodegenerative diseases and ovarian dysfunction, with an increasing number of reports on psychiatric disorders in recent years. Neuroimaging studies show that abnormalities in the amygdala and hippocampus are associated with neuropsychiatric disorders in adult FMR1 premutation carriers. FMRP may play a key role in the pathophysiology of psychiatric symptoms in this population.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
David E. Godler, Yoshimi Inaba, Minh Q. Bui, David Francis, Cindy Skinner, Charles E. Schwartz, David J. Amor
Summary: This study characterizes the specific DNA methylation patterns of fragile X syndrome in blood and brain tissues, providing a novel avenue for the detection of the syndrome through DNA methylation analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Bonnie Poteet, Nadia Ali, Cecelia Bellcross, Stephanie L. Sherman, Whitney Espinel, Heather Hipp, Emily G. Allen
Summary: This study aimed to identify barriers and facilitators to receiving a FXPOI diagnosis and follow-up care. Interviews revealed that FXPOI patients often face issues such as lack of clinician awareness, absence of clear clinical treatment guidelines, and difficulty finding centralized sources of care.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2023)
Article
Multidisciplinary Sciences
Devan Straub, Lauren M. Schmitt, Anna E. Boggs, Paul S. Horn, Kelli C. Dominick, Christina Gross, Craig A. Erickson
Summary: Fragile X syndrome (FXS) is the most common inherited intellectual disability caused by a trinucleotide repeat expansion in the FMR1 gene. Current therapies are inefficient and the disease severity varies, making it difficult to predict disease trajectory and treatment response. A study found that a subset of males with FXS express low levels of FMRP, which contributes to phenotypic variability. A sensitive qRT-PCR assay was developed to detect FMR1 mRNA in blood, confirming the presence of trace amounts of FMR1 mRNA in some FXS patients and suggesting the need for better molecular assays for diagnosis.
SCIENTIFIC REPORTS
(2023)
Article
Psychiatry
Sarah J. White, Denise Gerber, Romina D. Sanchez Hernandez, Anthonia Efiannayi, Ishita Chowdhury, Hannah Partington, Joanna F. Moss
Summary: Research on women with the fragile-X premutation has shown that they have an increased risk for autistic traits and anxiety, which is specifically related to the presence of the premutation and not fully explained by maternal status or the stress of caring for children with neurodevelopmental disorders.
BRITISH JOURNAL OF PSYCHIATRY
(2021)
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
Biology
Osnat Segal, Tamar Kowal, Yonit Banet-Levi, Lidia V. Gabis
Summary: This study is among the first to investigate executive functions and phonological memory in females with the Fragile X premutation. The results showed that females carrying the premutation of the FMR1 gene reported lower executive functions compared to the control group in the BRIEF questionnaire. Additionally, a relationship was found between the number of CGG sequence repeats and nonword repetitions and forward digit span.
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
Genetics & Heredity
Essra Bartlett, Alison D. Archibald, David Francis, Ling Ling, Rob Thomas, Gabrielle Chandler, Lisa Ward, Gemma O'Farrell, Alison Pandelache, Martin B. Delatycki, Bruce H. Bennetts, Gladys Ho, Katrina Fisk, Emma K. Baker, David J. Amor, David E. Godler
Summary: The FMR1 premutation can lead to FXTAS and FXS when maternally transmitted, with post-zygotic paternal retraction resulting in low-level mosaicism for normal size alleles. These normal alleles remain functional when passed over multiple generations.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
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)