scholarly journals Autism Profiles of Males With Fragile X Syndrome

2008 ◽  
Vol 113 (6) ◽  
pp. 427-438 ◽  
Author(s):  
Susan W. Harris ◽  
David Hessl ◽  
Beth Goodlin-Jones ◽  
Jessica Ferranti ◽  
Susan Bacalman ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Autism Diagnosis ◽  
Cgg Repeat ◽  
Molecular Features ◽  
Fmr1 Mrna ◽  
Two Measures ◽  
Dsm Iv ◽  
Relationship Of ◽  
The Relationship

Abstract Autism, which is common in individuals with fragile X syndrome, is often difficult to diagnose. We compared the diagnostic classifications of two measures for autism diagnosis, the ADOS and the ADI-R, in addition to the DSM-IV-TR in 63 males with this syndrome. Overall, 30% of the subjects met criteria for autistic disorder and 30% met criteria for PDD-NOS. The classifications on the ADOS and DSM-IV-TR were most similar, whereas the ADI-R classified subjects as autistic much more frequently. We further investigated the relationship of both FMRP and FMR1 mRNA to symptoms of autism in this cohort and found no significant relationship between the measures of autism and molecular features, including FMRP, FMR1 mRNA, and CGG repeat number.

scholarly journals Targeted Reactivation of FMR1 Transcription in Fragile X Syndrome Embryonic Stem Cells

2018 ◽  
Author(s):  
Jill M. Haenfler ◽  
Geena Skariah ◽  
Caitlin M. Rodriguez ◽  
Andre Monteiro da Rocha ◽  
Jack M. Parent ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Embryonic Stem ◽  
Transcriptional Silencing ◽  
Hesc Line ◽  
Human Patient ◽  
Cgg Repeat ◽  
Heterochromatin Formation ◽  
Fmr1 Mrna

ABSTRACTFragile X Syndrome (FXS) is the most common inherited cause of intellectual disability and autism. It results from expansion of a CGG nucleotide repeat in the 5’ untranslated region of FMR1. Large expansions elicit repeat and promoter hyper-methylation, heterochromatin formation, FMR1 transcriptional silencing, and loss of the Fragile X protein, FMRP. Efforts aimed at correcting the sequelae resultant from FMRP loss have thus far proven insufficient, perhaps because of FMRP’s pleiotropic functions. As the repeats do not disrupt the FMRP coding sequence, reactivation of endogenous FMR1 gene expression could correct the proximal event in FXS pathogenesis. Here we utilize the CRISPR/dCAS9 system to selectively re-activate transcription from the silenced FMR1 locus. Fusion of the transcriptional activator VP192 to dCAS9 robustly enhances FMR1 transcription and increases FMRP levels when targeted directly to the CGG repeat in human cells. Using a previously uncharacterized FXS human embryonic stem cell (hESC) line which acquires transcriptional silencing with serial passaging, we achieved locus-specific transcriptional re-activation of FMR1 mRNA expression despite promoter and repeat methylation. These studies demonstrate that FMR1 mRNA expression can be selectively reactivated in human patient cells, creating a pathway forward for therapeutic development in Fragile X Syndrome.

Health Supervision for Children With Fragile X Syndrome

PEDIATRICS ◽  
1996 ◽  
Vol 98 (2) ◽  
pp. 297-300
Author(s):  
Keyword(s):  
Mental Retardation ◽  
Developmental Delay ◽  
Fragile X Syndrome ◽  
X Chromosome ◽  
Dna Analysis ◽  
Fragile Site ◽  
Fragile X ◽  
Physical Features ◽  
Relationship Of ◽  
The Relationship

This set of guidelines is designed to assist pediatricians in caring for children with fragile X syndrome confirmed by DNA analysis (Table). Occasionally pediatricians are called on to advise a pregnant woman who has been informed of a prenatal diagnosis of fragile X syndrome. Therefore, guidelines are also offered for this situation. Fragile X syndrome is usually diagnosed during childhood and is characterized by developmental delay or mental retardation, characteristic physical features, and abnormal behavioral patterns.1,2 The distinctive fragile site on the X chromosome was first described in 1969 as a discontinuous site on the long arm of the X chromosome present after cell culture under folate-deficient conditions. In 1977 the relationship of this site to X-linked mental retardation was noted, and fragile X syndrome began to be defined. Since that time, the cytogenetic, molecular, and clinical features of the condition have been more clearly defined,3 and it is now recognized as the most common hereditary cause of mental retardation. Its frequency has been estimated to be approximately per 2500 to 1 per 1250 males and 1 per 5000 to 1 per 1600 females. The phenotype of fragile X syndrome in males often has a number of distinctive, recognizable features, including developmental delay or mental retardation, a prominent forehead, a long, thin face and a prominent jaw that appear late in childhood or early adolescence, large protuberant and slightly dysmorphic ears, and the presence of or ultimate development of macro-orchidism. This phenotype can be very subtle, is not always apparent, and becomes more identifiable with age.2

scholarly journals The Contribution of Pluripotent Stem Cell (PSC)-Based Models to the Study of Fragile X Syndrome (FXS)

2019 ◽  
Vol 9 (2) ◽  
pp. 42 ◽  
Author(s):  
Manar Abu Diab ◽  
Rachel Eiges
Keyword(s):  
Stem Cells ◽  
Gene Silencing ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Embryonic Stem ◽  
Cgg Repeat ◽  
Molecular Features ◽  
Epigenetic Gene Silencing ◽  
Mental Retardation Protein ◽  
Induced Pluripotent

Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a deficiency in the fragile X mental retardation protein (FMRP) due to a CGG repeat expansion in the 5′-UTR of the X-linked FMR1 gene. When CGGs expand beyond 200 copies, they lead to epigenetic gene silencing of the gene. In addition, the greater the allele size, the more likely it will become unstable and exhibit mosaicism for expansion size between and within tissues in affected individuals. The timing and mechanisms of FMR1 epigenetic gene silencing and repeat instability are far from being understood given the lack of appropriate cellular and animal models that can fully recapitulate the molecular features characteristic of the disease pathogenesis in humans. This review summarizes the data collected to date from mutant human embryonic stem cells, induced pluripotent stem cells, and hybrid fusions, and discusses their contribution to the investigation of FXS, their key limitations, and future prospects.

scholarly journals Do Children With Fragile X Syndrome Show Declines or Plateaus in Adaptive Behavior?

2015 ◽  
Vol 120 (5) ◽  
pp. 412-432 ◽  
Author(s):  
Laura J. Hahn ◽  
Nancy C. Brady ◽  
Steven F. Warren ◽  
Kandace K. Fleming
Keyword(s):  
Fragile X Syndrome ◽  
Adaptive Behavior ◽  
Cognitive Abilities ◽  
Fragile X ◽  
Vineland Adaptive Behavior Scales ◽  
Autistic Behavior ◽  
Relationship Of ◽  
The Relationship ◽  
Autistic Behaviors ◽  
Vineland Adaptive Behavior

Abstract This study explores if children with fragile X syndrome (FXS) show advances, declines, or plateaus in adaptive behavior over time and the relationship of nonverbal cognitive abilities and autistic behavior on these trajectories. Parents of 55 children with FXS completed the Vineland Adaptive Behavior Scales (Sparrow, Balla, & Cicchetti, 1984; Sparrow, Cicchetti, & Balla, 2005) between 3 and 6 times from 2 to 10 years of age. Using raw scores, results indicate that about half of the sample showed advances in adaptive behavior, whereas the other half showed declines, indicating a regression in skills. Children who were more cognitively advanced and had less autistic behaviors had higher trajectories. Understanding the developmental course of adaptive behavior in FXS has implications for educational planning and intervention, especially for those children showing declines.

scholarly journals The Feasibility and Utility of Hair Follicle Sampling To Measure FMRP and FMR1 mRNA in Children With or Without Fragile X Syndrome

2021 ◽  
Author(s):  
Isha Jalnapurkar ◽  
Jean A. Frazier ◽  
Mark Roth ◽  
David M. Cochran ◽  
Ann Foley ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Hair Follicle ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Hair Follicles ◽  
Buccal Swab ◽  
Typically Developing ◽  
Cgg Repeat ◽  
Fragile X Mental Retardation ◽  
Fmr1 Mrna

Abstract Background: Fragile X syndrome (FXS) is the most common cause inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (>200 base pairs) on the promotor region of the fragile X mental retardation 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, Fragile X mental retardation protein (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 and FMRP. Methods: Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. Results: There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants, and lowest in the FXS boys. Measurement of FMR1 and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. Conclusion: Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home and office settings, is feasible, repeatable, and can be used for measurement of FMR1 and FMRP in longitudinal studies.

scholarly journals Study of the Interaction between Executive Function and Adaptive Behavior at School in Girls with Fragile X Syndrome

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1108
Author(s):  
Lorena Joga-Elvira ◽  
Jennifer Martinez-Olmo ◽  
María-Luisa Joga ◽  
Carlos Jacas ◽  
Ana Roche-Martínez ◽  
...  
Keyword(s):  
Executive Function ◽  
Executive Functions ◽  
Fragile X Syndrome ◽  
Adaptive Behavior ◽  
Neuropsychological Tests ◽  
Rating Scale ◽  
Fragile X ◽  
School Setting ◽  
Control Group ◽  
The Relationship

The aim of this research is to analyze the relationship between executive functions and adaptive behavior in girls with Fragile X syndrome (FXS) in the school setting. This study is part of a larger investigation conducted at the Hospital Parc Tauli in Sabadell. The sample consists of a total of 40 girls (26 with FXS and 14 control) aged 7–16 years, who were administered different neuropsychological tests (WISC-V, NEPSY-II, WCST, TOL) and questionnaires answered by teachers (ABAS-II, BRIEF 2, ADHD Rating Scale). The results show that there is a greater interaction between some areas of executive function (cognitive flexibility, auditory attention, and visual abstraction capacity) and certain areas of adaptive behavior (conceptual, practical, social, and total domains) in the FXS group than in the control group. These results suggest that an alteration in the executive functions was affecting the daily functioning of the girls with FXS to a greater extent.

Learning-disabled Males With a Fragile X CGG Expansion in the Upper Premutation Size Range

PEDIATRICS ◽  
1996 ◽  
Vol 97 (1) ◽  
pp. 122-126
Author(s):  
Randi J. Hagerman ◽  
Louise W. Staley ◽  
Rebecca O'Conner ◽  
Kellie Lugenbeel ◽  
David Nelson ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Size Range ◽  
Cpg Island ◽  
Fragile X ◽  
Learning Disabled ◽  
Full Mutation ◽  
Cgg Repeat ◽  
Responsible Gene ◽  
Repeat Segment

There is a broad spectrum of clinical involvement in both boys and girls affected by fragile X syndrome. Although this disorder is best known as the most common inherited cause of mental retardation, it also can manifest as learning disabilities in individuals with IQs in the broad range of normal. Boys are usually retarded, and girls are usually learning disabled with fragile X syndrome.1 The responsible gene, fragile X mental retardation 1 (FMR1), was isolated in 1991, and the mutation was found to involve expansion of a trinucleotide (CGG) repeat segment. Individuals with fragile X syndrome have a CGG expansion of more than 200 repeats associated with hypermethylation of both the expansion and an adjacent CpG island (full mutation).2,3

The Risk Tolerance Measure in the 2016 Survey of Consumer Finances: New, But Is It Improved?

2021 ◽  
pp. JFCP-19-00022
Author(s):  
Kyoung Tae Kim ◽  
Sherman D. Hanna ◽  
Dongyue Ying
Keyword(s):  
Negative Relationship ◽  
Risk Tolerance ◽  
Stock Ownership ◽  
Survey Of Consumer Finances ◽  
Consumer Finances ◽  
Two Measures ◽  
Complex Patterns ◽  
Relationship Of ◽  
The Relationship ◽  
Different Levels

The Survey of Consumer Finances (SCF) has included a 4-level risk tolerance measure since 1983. In 2016, the SCF also included an 11-level risk tolerance measure. We compare the two measures, and develop suggestions for using the new measure. While the new measure is seemingly simpler than the old measure, we demonstrate that it does not have a monotonic relationship with owning stock assets, with a pattern similar to the relationship of the old measure to stock ownership. We also identify complex patterns of factors related to different levels of the new measure, for instance education has a negative relationship at one level but positive at another level. Those using the new measure should consider the complex patterns we demonstrate.

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