Analyzing the Quality of Life in Individuals with Fragile X Syndrome in Relation to Sleep and Mental Health
This study included 119 individuals with Fragile X Syndrome who were given different cognitive examinations by a neuropsychologist or by parent-proxy questionnaires. This study focused on the Pediatric Quality of Life Inventory (PedsQoL), the Anxiety, Depression and Mood Scale (ADAMS), the Children's Sleep Habits Questionnaire (CSHQ), but did include other cognitive tests (Vineland Adaptive Behaviour Scales, Nonverbal IQ, Autism Diagnostic Observation Schedule). We identified significant associations between decreases in emotional, social and school domains of PedsQoL and the ADAMS subtests of Generalized Anxiety, Manic/Hy...
Source: Journal of Autism and Developmental Disorders - April 23, 2024 Category: Psychiatry Authors: Amrita Minhas Kerri Whitlock Cory Rosenfelt Julie Shatto Brittany Finlay Jennifer Zwicker Sarah Lippe Sebastien Jacquemont Randi Hagerman Kara Murias Francois V Bolduc Source Type: research
Purinergic Signalling Mediates Aberrant Excitability of Developing Neuronal Circuits in the Fmr1 Knockout Mouse Model
In this study, we examined whether elevated astrocyte purinergic signalling also impacts neuronal morphology and connectivity ofFmr1 KO cortical neurons. Here, we found that conditioned media from primaryFmr1 KO astrocytes was sufficient to enhance neurite extension and complexity of both wildtype andFmr1 KO neurons to a similar degree as UTP-mediated outgrowth. Significantly enhanced firing was also observed inFmr1 KO neuron-astrocyte co-cultures grown on microelectrode arrays but was associated with large deficits in firing synchrony. The selective P2Y2 purinergic receptor antagonist AR-C 118925XX effectively normalized ...
Source: Molecular Neurobiology - April 23, 2024 Category: Neurology Source Type: research
Conformational and dynamic properties of the KH1 domain of FMRP and its fragile X syndrome linked G266E variant
This study aims to elucidate the molecular mechanism underlying the loss of function associated with the G266EKH1 pathological variant. We investigate the conformational and dynamical properties of the isolated KH1 domain and the two KH1 site-directed mutants G266EKH1 and G266AKH1. Employing a combined in vitro and in silico approach, we reveal that the G266EKH1 variant lacks the characteristic features of a folded domain. This observation provides an explanation for functional impairment observed in FMRP carrying the G266E mutation within the KH1 domain, as it renders the domain unable to fold properly. Molecular Dynamics...
Source: Biochimica et Biophysica Acta - April 19, 2024 Category: Biochemistry Authors: Flavia Catalano Daniele Santorelli Alessandra Astegno Filippo Favaretto Marco D'Abramo Alessandra Del Giudice Maria Laura De Sciscio Francesca Troilo Giorgio Giardina Adele Di Matteo Carlo Travaglini-Allocatelli Source Type: research
Phenotypic analysis of multielectrode array EEG biomarkers in developing and adult male Fmr1 KO mice
Neurobiol Dis. 2024 Apr 4:106496. doi: 10.1016/j.nbd.2024.106496. Online ahead of print.ABSTRACTFragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent electroencephalographic (EEG) studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced phase locking of sound-evoked gamma oscillations. Similar EEG phenotypes are present in mouse models of FXS, but very little is known about...
Source: Neurobiology of Disease - April 6, 2024 Category: Neurology Authors: Carrie R Jonak Samantha A Assad Manbir S Sandhu Terese A Garcia Jeffrey A Rumschlag Khaleel A Razak Devin K Binder Source Type: research
Mitochondrial dysfunction in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients
Mol Biol Rep. 2024 Apr 5;51(1):480. doi: 10.1007/s11033-024-09415-7.ABSTRACTFragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene. FXTAS is associated with elevated levels of FMR1 mRNA, leading to neurodegenerative manifestations such as tremors and ataxia.Mounting evidence sugg...
Source: Molecular Biology Reports - April 5, 2024 Category: Molecular Biology Authors: Giovanni Pagano Alex Lyakhovich Federico V Pallard ó Luca Tiano Adriana Zatterale Marco Trifuoggi Source Type: research
Mitochondrial dysfunction in Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome: prospect use of antioxidants and mitochondrial nutrients
Mol Biol Rep. 2024 Apr 5;51(1):480. doi: 10.1007/s11033-024-09415-7.ABSTRACTFragile X syndrome (FXS) is a genetic disorder characterized by mutation in the FMR1 gene, leading to the absence or reduced levels of fragile X Messenger Ribonucleoprotein 1 (FMRP). This results in neurodevelopmental deficits, including autistic spectrum conditions. On the other hand, Fragile X-associated tremor/ataxia syndrome (FXTAS) is a distinct disorder caused by the premutation in the FMR1 gene. FXTAS is associated with elevated levels of FMR1 mRNA, leading to neurodegenerative manifestations such as tremors and ataxia.Mounting evidence sugg...
Source: Molecular Biology Reports - April 5, 2024 Category: Molecular Biology Authors: Giovanni Pagano Alex Lyakhovich Federico V Pallard ó Luca Tiano Adriana Zatterale Marco Trifuoggi Source Type: research
Clinical application value of pre-pregnancy carrier screening in Chinese Han childbearing population
CONCLUSION: Monogenic recessive hereditary diseases had a high carrier rate in the population. Pre-pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis could provide more precise reproductive choices for high-risk parents.PMID:38562051 | DOI:10.1002/mgg3.2425 (Source: Molecular Medicine)
Source: Molecular Medicine - April 2, 2024 Category: Molecular Biology Authors: Li Tan Yuefan Qi Peijuan Zhao LanLan Cheng Guo Yu Dongmei Zhao Yu Xia Song Yun Gai Xiang Source Type: research
Clinical application value of pre-pregnancy carrier screening in Chinese Han childbearing population
CONCLUSION: Monogenic recessive hereditary diseases had a high carrier rate in the population. Pre-pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis could provide more precise reproductive choices for high-risk parents.PMID:38562051 | PMC:PMC10985407 | DOI:10.1002/mgg3.2425 (Source: Molecular Medicine)
Source: Molecular Medicine - April 2, 2024 Category: Molecular Biology Authors: Li Tan Yuefan Qi Peijuan Zhao LanLan Cheng Guo Yu Dongmei Zhao Yu Xia Song Yun Gai Xiang Source Type: research
Clinical application value of pre ‐pregnancy carrier screening in Chinese Han childbearing population
ConclusionMonogenic recessive hereditary diseases had a high carrier rate in the population. Pre-pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis could provide more precise reproductive choices for high-risk parents. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - April 2, 2024 Category: Genetics & Stem Cells Authors: Li Tan,
Yuefan Qi,
Peijuan Zhao,
LanLan Cheng,
Guo Yu,
Dongmei Zhao,
Yu Xia Song,
Yun Gai Xiang Tags: ORIGINAL ARTICLE Source Type: research
Proteomics insights into fragile X syndrome: Unraveling molecular mechanisms and therapeutic avenues
Neurobiol Dis. 2024 Mar 26:106486. doi: 10.1016/j.nbd.2024.106486. Online ahead of print.ABSTRACTFragile X Syndrome (FXS) is a neurodevelopment disorder characterized by cognitive impairment, behavioral challenges, and synaptic abnormalities, with a genetic basis linked to a mutation in the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene that results in a deficiency or absence of its protein product, Fragile X Messenger Ribonucleoprotein (FMRP). In recent years, mass spectrometry (MS) - based proteomics has emerged as a powerful tool to uncover the complex molecular landscape underlying FXS. This review provides a comp...
Source: Neurobiology of Disease - March 28, 2024 Category: Neurology Authors: Diana A Abbasi Elizabeth Berry-Kravis Xinyu Zhao Stephanie M Cologna Source Type: research
Proteomics insights into fragile X syndrome: Unraveling molecular mechanisms and therapeutic avenues
Neurobiol Dis. 2024 Mar 26:106486. doi: 10.1016/j.nbd.2024.106486. Online ahead of print.ABSTRACTFragile X Syndrome (FXS) is a neurodevelopment disorder characterized by cognitive impairment, behavioral challenges, and synaptic abnormalities, with a genetic basis linked to a mutation in the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene that results in a deficiency or absence of its protein product, Fragile X Messenger Ribonucleoprotein (FMRP). In recent years, mass spectrometry (MS) - based proteomics has emerged as a powerful tool to uncover the complex molecular landscape underlying FXS. This review provides a comp...
Source: Neurobiology of Disease - March 28, 2024 Category: Neurology Authors: Diana A Abbasi Elizabeth Berry-Kravis Xinyu Zhao Stephanie M Cologna Source Type: research
FMRP expression correlates with IQ in both PBMCs and fibroblasts from individuals with a FMR1 mutation
Fragile X syndrome (FXS) is the most common heritable form of intellectual disability and is caused by CGG repeat expansions exceeding 200 (full mutation). Such expansions lead to hypermethylation and transcriptional silencing of the Fragile X messenger ribonucleoprotein 1 (FMR1) gene. As a consequence, little or no FMR1 protein (FMRP) is produced; absence of the protein, which normally is responsible for neuronal development and maintenance, causes the syndrome. Previous studies have demonstrated the causal relationship between FMRP levels and cognitive abilities in peripheral blood mononuclear cells (PBMCs) and dermal fi...
Source: Journal of Molecular Diagnostics - March 21, 2024 Category: Pathology Authors: Poonnada Jiraanont, Marwa Zafarullah, Noor Sulaiman, Glenda M. Espinal, Jamie L. Randol, Blythe Durbin-Johnson, Andrea Schneider, Randi J. Hagerman, Paul J. Hagerman, Flora Tassone Tags: Regular Article Source Type: research
FMR1 Protein Expression Correlates with Intelligence Quotient in Both Peripheral Blood Mononuclear Cells and Fibroblasts from Individuals with an FMR1 Mutation
Fragile X syndrome (FXS) is the most common heritable form of intellectual disability and is caused by CGG repeat expansions exceeding 200 (full mutation). Such expansions lead to hypermethylation and transcriptional silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene. As a consequence, little or no FMR1 protein (FMRP) is produced; absence of the protein, which normally is responsible for neuronal development and maintenance, causes the syndrome. Previous studies have demonstrated the causal relationship between FMRP levels and cognitive abilities in peripheral blood mononuclear cells (PBMCs) and dermal fi...
Source: Journal of Molecular Diagnostics - March 21, 2024 Category: Pathology Authors: Poonnada Jiraanont, Marwa Zafarullah, Noor Sulaiman, Glenda M. Espinal, Jamie L. Randol, Blythe Durbin-Johnson, Andrea Schneider, Randi J. Hagerman, Paul J. Hagerman, Flora Tassone Tags: Regular article Source Type: research
Differential cognitive and behavioral development from 6 to 24 months in autism and fragile X syndrome
ConclusionsOur results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive develo pment in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups. (Source: Journal of Neurodevelopmental Disorders)
Source: Journal of Neurodevelopmental Disorders - March 20, 2024 Category: Neurology Source Type: research
Genes, Vol. 15, Pages 356: Variation of FMRP Expression in Peripheral Blood Mononuclear Cells from Individuals with Fragile X Syndrome
This study underscores the complexity of FMR1 allelotypes and FMRP expression and prompts a reevaluation of FXS therapies aimed at reactivating large full mutation alleles that are likely not capable of producing sufficient FMRP to improve cognitive function. (Source: Genes)
Source: Genes - March 13, 2024 Category: Genetics & Stem Cells Authors: Jamie L. Randol Kyoungmi Kim Matthew D. Ponzini Flora Tassone Alexandria K. Falcon Randi J. Hagerman Paul J. Hagerman Tags: Article Source Type: research
