scholarly journals Family as a Context for Child Development: Mothers with the FMR1 Premutation and Their Children with Fragile X Syndrome

2021 ◽  
Vol 42 (04) ◽  
pp. 277-286
Author(s):  
Katherine Bangert ◽  
Carly Moser ◽  
Laura Friedman ◽  
Jessica Klusek
Keyword(s):  
Fragile X Syndrome ◽  
Family Environment ◽  
Fragile X ◽  
Genetic Disorder ◽  
Challenging Behaviors ◽  
Fmr1 Gene ◽  
Fmr1 Premutation ◽  
Children And Parents ◽  
Increased Risk ◽  
Outcomes For Children

AbstractFragile X syndrome (FXS) is a genetic disorder caused by changes of the FMR1 gene that is passed along among families. A range of developmental processes may be impacted with wide variation in abilities across individuals with FXS. Mothers of children with FXS are often carriers of a “premutation” expansion on the FMR1 gene, which is associated with its own clinical phenotype. These maternal features may increase individual and family vulnerabilities, including increased risk for depression and anxiety disorders and difficulties in social and cognitive ability. These characteristics may worsen with age, and potentially interact with a child's challenging behaviors and with family dynamics. Thus, families of children with FXS may experience unique challenges related to genetic risk, manifested across both children and parents, that should be considered in therapeutic planning to optimize outcomes for children and their families. In this article, we review core features of the FMR1 premutation as expressed in mothers and aspects of the family environment that interface with developmental outcomes of children with FXS. Recommendations for family-centered support services are discussed.

scholarly journals Infant Temperament in the FMR1 Premutation and Fragile X Syndrome

2018 ◽  
Vol 48 (3) ◽  
pp. 412-422
Author(s):  
Bridgette L. Tonnsen ◽  
Anne C. Wheeler ◽  
Lisa R. Hamrick ◽  
Jane E. Roberts
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Infant Temperament ◽  
Fmr1 Premutation

Roles of ZF5 and CGGBP-20 transcription factors in regulating expression of human FMR1 gene responsible for fragile X-syndrome

2010 ◽  
Vol 4 (1) ◽  
pp. 54-62 ◽  
Author(s):  
P. V. Gulyy ◽  
S. V. Orlov ◽  
E. B. Dizhe ◽  
K. B. Kuteikin-Teplyakov ◽  
I. A. Ignatovich ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Fmr1 Gene

scholarly journals Analysis of unstable DNA sequence in FMR1 gene in Polish families with fragile X syndrome.

1996 ◽  
Vol 43 (2) ◽  
pp. 383-388
Author(s):  
M Milewski ◽  
M Zygulska ◽  
J Bal ◽  
W H Deelen ◽  
E Obersztyn ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Dna Sequence ◽  
Clinical Features ◽  
Fragile Site ◽  
Fragile X ◽  
Fmr1 Gene ◽  
Repeat Number ◽  
Full Mutation ◽  
Cgg Repeats ◽  
Large Expansion

The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGG repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted.

scholarly journals Autoimmune disease in mothers with the FMR1 premutation is associated with seizures in their children with fragile X syndrome

2010 ◽  
Vol 128 (5) ◽  
pp. 539-548 ◽  
Author(s):  
Weerasak Chonchaiya ◽  
Flora Tassone ◽  
Paul Ashwood ◽  
David Hessl ◽  
Andrea Schneider ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Fmr1 Premutation

scholarly journals Transcriptional Reactivation of the FMR1 Gene. A Possible Approach to the Treatment of the Fragile X Syndrome

Genes ◽  
2016 ◽  
Vol 7 (8) ◽  
pp. 49 ◽  
Author(s):  
Elisabetta Tabolacci ◽  
Federica Palumbo ◽  
Veronica Nobile ◽  
Giovanni Neri
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Fmr1 Gene ◽  
Transcriptional Reactivation

scholarly journals Identification of microRNAs Associated With Human Fragile X Syndrome Using Next Generation Sequencing

2021 ◽  
Author(s):  
Maryam Sotoudeh Anvari ◽  
Hamed Vasei ◽  
Hossein Najmabadi ◽  
Reza Shervin Badv ◽  
Akram Gholipour ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Fragile X Syndrome ◽  
Deep Sequencing ◽  
Neurological Disorders ◽  
Fragile X ◽  
Expression Profiles ◽  
Fmr1 Gene ◽  
Blood Samples ◽  
Generation Sequencing ◽  
Potential Biomarkers

Abstract Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene which can lead to a loss or shortage of the FMR1 protein. This protein interacts with specific miRNAs, and a change can cause a range of neurological disorders. Therefore, miRNAs could act as a novel class of potential biomarkers for common CNS diseases. The aim of this study was to test this theory by exploring the expression profiles of various miRNAs in Iranian FXS patients using deep sequencing-based technologies, and validate the miRNAs affecting expression of the FMR1 gene. Blood samples were taken from 15 patients with FXS (9 males, 6 females) and 12 controls. 25 miRNAs were differentially expressed in individuals with FXS compared to controls. Levels of 9 miRNAs were found to be significantly changed (3 upregulated and 6 downregulated). In FXS patients, the levels of hsa-miR-532-5p, hsa-miR-652-3p and hsa-miR-4797-3p were significantly upregulated while levels of hsa-miR-191-5p, hsa-miR-181-5p, hsa-miR-26a-5p, hsa-miR-30e-5p, hsa-miR-186-5p, and hsa-miR-4797-5p exhibited significant downregulation; and these dysregulations were confirmed by RT‐qPCR. This study present altered miRNA expression in blood samples from FXS patients, which could be used for diagnostic, prognostic, and treatment purposes. Larger studies are required to confirm these preliminary results.

scholarly journals Computational analysis of transcriptome signature repurposes low dose trifluoperazine for the treatment of fragile X syndrome in mouse model

2019 ◽  
Author(s):  
Qi Ding ◽  
Ferzin Sethna ◽  
Xue-Ting Wu ◽  
Zhuang Miao ◽  
Ping Chen ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Computational Analysis ◽  
Low Dose ◽  
Fragile X ◽  
Genetic Disorder ◽  
Gene Signature ◽  
Signature Database ◽  
Therapeutic Value ◽  
Elevated Activity ◽  
Potential Therapeutic Intervention

ABSTRACTFragile X syndrome (FXS), caused by mutations in fragile X mental retardation 1 gene (FMR1), is a prevailing genetic disorder of intellectual disability and autism. Currently, there is no efficacious medication for FXS. Here, we use transcriptome landscape as a holistic molecular phenotype/endpoint to identify potential therapeutic intervention. Through in silico screening with public gene signature database, computational analysis of transcriptome profile in Fmr1 knockout (KO) neurons predicts therapeutic value of an FDA-approved drug trifluoperazine. Through experimental validation, we find that systemic administration of low dose trifluoperazine at 0.05 mg/kg attenuates multiple FXS- and autism-related behavioral symptoms. Moreover, computational analysis of transcriptome alteration caused by trifluoperazine suggests a new mechanism of action against PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) activity. Consistently, trifluoperazine suppresses PI3K activity and its down-stream targets Akt (protein kinase B) and S6K1 (S6 kinase 1) in neurons. Further, trifluoperazine normalizes the aberrantly elevated activity of Akt and S6K1 and enhanced protein synthesis in FXS mouse. In conclusion, our data demonstrate promising value of gene signature-based computation in identification of therapeutic strategy and repurposing drugs for neurological disorders, and suggest trifluoperazine as a potential practical treatment for FXS.

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