Clinical Characteristics of Fragile X Syndrome Patients in                    Japan

Okazaki, Taro; Adachi, Kaori; Matsuura, Kaori; Oyama, Yoshitaka; Nose, Madoka; Shirahata, Emi; Abe, Toshiaki; Hasegawa, Takeshi; Maihara, Toshiro; Maegaki, Yoshihiro; Nanba, Eiji

doi:10.33160/yam.2021.02.005

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…Neuroimaging studies of FXS patients revealed several alterations in brain morphology, including brain overgrowth and increased size of lateral ventricles (Hazlett et al, 2012; Hunter et al, 2014; Hustyi et al, 2014; Okazaki et al, 2021). Given the robust astrogenesis in early brain development, exaggerated astrocyte proliferation may contribute to macrocephaly in FXS patients.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated cholesterol metabolism, aberrant excitability and altered cell cycle of astrocytes in fragile X syndrome

Ren

Burkovetskaya

Jung

et al. 2023

Glia

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Fragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by the transcriptional silencing of the FMR1 gene. While neuronal contribution to FXS has been extensively studied in both animal and human‐based models of FXS, the roles of astrocytes, a type of glial cells in the brain, are largely unknown. Here, we generated a human‐based FXS model via differentiation of astrocytes from human‐induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) and characterized their development, function, and proteomic profiles. We identified shortened cell cycle, enhanced Ca2+ signaling, impaired sterol biosynthesis, and pervasive alterations in the proteome of FXS astrocytes. Our work identified astrocytic impairments that could contribute to the pathogenesis of FXS and highlight astrocytes as a novel therapeutic target for FXS treatment.

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Section: Discussionmentioning

confidence: 99%

Dysregulated cholesterol metabolism, aberrant excitability and altered cell cycle of astrocytes in fragile X syndrome

Ren

Burkovetskaya

Jung

et al. 2023

Glia

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“…In addition, we found that some facial features were common, such as a long palpebral fissure (58%), a broad or prominent forehead (53%), and periorbital puffiness (39%). Several studies in Japan, Thailand, and Korea reported the facial features of FXS, and some in these countries also found the elongated facial characteristic of FXS to be less significant than that of the American population ( 28 , 29 ). In sum, the statistics of facial features are subjective to some extent and the facial features become more obvious and noticeable with age.…”

Section: Discussionmentioning

confidence: 99%

The incidence and clinical characteristics of fragile X syndrome in China

Mei

Hu²,

Li³

et al. 2023

Front. Pediatr.

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IntroductionFragile X syndrome (FXS) is a X-linked neurodevelopmental disorder (NDD). This study aims to investigate the incidence of FXS in Chinese children and analyze the comprehensive clinical characteristics of these FXS children.MethodsChildren diagnosed with idiopathic NDD were recruited between 2016 and 2021 from the department of Child Health Care, Children's Hospital of Fudan University. We combined tetraplet-primed PCR-capillary electrophoresis and whole exome sequencing (WES)/panel or array-based comparative genomic hybridization (array-CGH) to identify the size of the CGG repeats and the mutations or copy number variations (CNVs) in the genome and in FMR1. The clinical features of FXS children were analyzed according to pediatricians' recording, parental questionnaires, the results of examinations and follow-up.ResultsThe incidence of FXS in Chinese children with idiopathic NDD was 2.4% (42/1753) and in those with FXS, 2.38% had a deletion (1/42). Here, we present the clinical characteristics of 36 children with FXS. Overweight was observed in two boys. The average intelligence quotient (IQ)/development quotient (DQ) of all FXS patients was 48. The average ages of meaningful words and walking alone were 2 years and 10 months and 1 year and 7 months, respectively. The most frequent repetitive behavior was stimulated by hyperarousal to sensory stimulation. On social aspects, social withdrawal, social anxiety, and shyness accounted for 75%, 58%, and 56% of the total number of children, respectively. Approximately 60% of FXS children in this cohort were emotionally labile and prone to temper tantrums. Self-injury and aggression toward others could also be observed, at 19% and 28%, respectively. The most frequent behavioral problem was attention-deficit hyperactivity disorder (ADHD) seen in 64% and the most common facial features were a narrow and elongated face and large or prominent ears in 92% of patients.DiscussionScreening of FMR1 full mutation provides the possibility for patients' further medical supports and the clinical features of FXS children obtained in this study will increase the understanding and diagnosis of FXS.

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“…Fragile X syndrome (FXS) is the most common form of inherited intellectual disability that manifests with clinical features, including anxiety, autism symptoms, and poor attention, and physical features, including prominent ears, a long face, and hyperextensible finger joints (Hagerman et al, 2017;Niu et al, 2017;Bagni and Zukin, 2019;Okazaki et al, 2021). FXS is caused by a reduction in fragile X mental retardation protein (FMRP) expression levels.…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Polyadenylation Element-Binding Protein 1 Post-transcriptionally Regulates Fragile X Mental Retardation 1 Expression Through 3′ Untranslated Region in Central Nervous System Neurons

Hayashi

Tanaka

et al. 2022

Front. Cell. Neurosci.

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Fragile X syndrome (FXS) is an inherited intellectual disability caused by a deficiency in Fragile X mental retardation 1 (Fmr1) gene expression. Recent studies have proposed the importance of cytoplasmic polyadenylation element-binding protein 1 (CPEB1) in FXS pathology; however, the molecular interaction between Fmr1 mRNA and CPEB1 has not been fully investigated. Here, we revealed that CPEB1 co-localized and interacted with Fmr1 mRNA in hippocampal and cerebellar neurons and culture cells. Furthermore, CPEB1 knockdown upregulated Fmr1 mRNA and protein levels and caused aberrant localization of Fragile X mental retardation protein in neurons. In an FXS cell model, CPEB1 knockdown upregulated the mRNA levels of several mitochondria-related genes and rescued the intracellular heat shock protein family A member 9 distribution. These findings suggest that CPEB1 post-transcriptionally regulated Fmr1 expression through the 3′ untranslated region, and that CPEB1 knockdown might affect mitochondrial function.

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Clinical Characteristics of Fragile X Syndrome Patients in Japan

Cited by 4 publications

References 13 publications

Dysregulated cholesterol metabolism, aberrant excitability and altered cell cycle of astrocytes in fragile X syndrome

Dysregulated cholesterol metabolism, aberrant excitability and altered cell cycle of astrocytes in fragile X syndrome

The incidence and clinical characteristics of fragile X syndrome in China

Cytoplasmic Polyadenylation Element-Binding Protein 1 Post-transcriptionally Regulates Fragile X Mental Retardation 1 Expression Through 3′ Untranslated Region in Central Nervous System Neurons

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