Article

The relationship between fragile X syndrome, rett syndrome and autism spectrum disorders

Authors:
  • University Children's Hospital, Sofia, Bulgaria
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Abstract

Autism is a complex behaviorally-defined disorder of the immature brain. It is not a disease but a syndrome with multiple non genetic and/or genetic causes. Autism spectrum disorders (ASDs) are conditions which can be either isolated or syndromic, that is associated with other clinical features such as facial dysmorphism, limb or visceral malformations, and growth abnormalities. Currently, diagnosable medical conditions, cytogenetic abnormalities, environmental factors, and single-gene defects associated with autism, together account for 10-20% of cases. Rett (RTT) syndrome is an X-linked disorder that presents in females and is caused by mutations in the MECP2 gene. This syndrome is the only ASDs with a known genetic cause. Fragile X syndrome (FXS) is the most common cause of inherited mental retardation. It is caused by an expansion of a trinucleotide repeat region in the FMR1 gene found on the X chromosome. There has been extensive evidence in the literature that people with FXS are at an increased risk of having autism, although it is still unclear how or why these two disorders are related. The aim of our study was to perform genetic screening for FMR1 and MECP2 mutations in patients with idiopathic autism in order to provide precise diagnosis and adequate genetic counseling.

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... The exact causes of ASD are not known, and both genetic and environmental factors are suggested to contribute to ASD. Fragile X syndrome, Rett syndrome, or cytogenetic abnormalities are reported to be associated with ASD [30,31]. NLGN3, NLGN4X, and SHANK3 are synaptic genes, and the mutation of these genes is involved in idiopathic autism [32][33][34][35]. ...
... After completing the social behavioral test, the rats were sacrificed under deep pentobarbital anesthesia and the left and right prefrontal cortex were collected from each group and frozen quickly in liquid nitrogen, then stored at −80 • C until the extraction of the total RNA. The experimental protocols were approved by the Ethics Committee of the Animal Care and Experimentation Council of the National Institute for Environmental Studies (NIES), Japan (AE- [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]19 December 2019; AE-20-05, 9 March 2020). All efforts were made to minimize the number of animals used and their suffering. ...
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions, and repetitive behaviors. We aimed to examine autism-like behaviors and related gene expressions in rats exposed to diesel exhaust (DE)-origin secondary organic aerosol (DE-SOA) perinatally. Sprague–Dawley pregnant rats were exposed to clean air (control), DE, and DE-SOA in the exposure chamber from gestational day 14 to postnatal day 21. Behavioral phenotypes of ASD were investigated in 10~13-week-old offspring using a three-chambered social behavior test, social dominance tube test, and marble burying test. Prefrontal cortex was collected to examine molecular analyses including neurological and immunological markers and glutamate concentration, using RT-PCR and ELISA methods. DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior, and increased repetitive behavior. Serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) mRNAs were downregulated whereas interleukin 1 β (IL-β) and heme oxygenase 1 (HO-1) mRNAs were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was also increased significantly in DE-SOA-exposed male and female rats. Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior by modulating molecules such as neurological and immunological markers in rats.
... Etiology of ASD has not been known and both genetic and environmental factors are thought to contribute to ASD. Regarding genetic factors, Fragile X syndrome, Rett syndrome, Fragile-X syndrome or cytogenetic abnormalities are associated with ASD [31,32]. Mutation of synaptic genes like NLGN3 and NLGN4X or SHANK3 are involved with idiopathic autism [33][34][35][36][37]. ...
Preprint
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Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions and repetitive behaviors. The exact cause and mechanism of autism remains unknown. Both genetic and environmental factors may involve in ASD. In this study, we used diesel exhaust origin secondary organic aerosol (DE-SOA) as environmental pollutants. The aim of present study is to examine autism-like behaviors and related gene expressions in rats exposed to DE-SOA perinatally. Sprague-Dawley pregnant rats were exposed to clean air (control), diesel exhaust (DE) and DE-SOA in the exposure chamber for 5 h per day, 5days a week from gestational day 8 to postnatal day 21. At postnatal day 21, the male and female offspring rats were allocated into three different groups as follows: 1) rats exposed to clean filtered air; 2) rats exposed to DE; 3) rats exposed to DE-SOA. Social behaviors were investigated at 10~13-weeks-old rats using a 3-chambered social behavior test, social dominance tube test and marble burying test. Prefrontal cortex was collected under deep anesthesia to examine neurological and immunological markers, glutamate concentration, mast cell and microglia activation using real-time RT-PCR method, ELISA method and immunohistochemical analysis. Results: DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior and increased repetitive behavior compared with the control rats. The mRNA expression levels of serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) were down-regulated whereas interleukin 1 b (IL-b), and heme oxygenase 1 (HO-1) were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA compared to the control rats. In addition, the expression of mast cells and microglia marker ionized calcium-binding adapter molecule (Iba)1 were increased in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was increased significantly in the prefrontal cortex of both male and female rats exposed to DE-SOA. Conclusion: Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior in rats by modulating neurological and immunological markers in the prefrontal cortex.
... Etiology of ASD has not been known and both genetic and environmental factors are thought to contribute to ASD. Regarding genetic factors, Fragile X syndrome, Rett syndrome, Fragile-X syndrome or cytogenetic abnormalities are associated with ASD [31,32]. Mutation of synaptic genes like NLGN3 and NLGN4X or SHANK3 are involved with idiopathic autism [33][34][35][36][37]. ...
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Rett syndrome (RS; MIM 312750) is a severe neurological disorder affecting exclusively females. Its prevalence is about 1 in 10,000 female births, and it is a prominent cause of profound mental handicap in women. RS is caused by mutations in the X-linked methyl CpG-binding protein 2 (MECP2) gene. These mutations were initially thought to be lethal in males. However, MECP2 mutations are now frequently identified in mentally retarded male patients. The frequency of disease-causing MECP2 mutations in this population is between 1.3% and 1.7%. Surprisingly, MECP2 mutations in males are responsible for a wide spectrum of neurological disorders, ranging from mild mental retardation to severe neonatal encephalopathy. The aim of this review is to describe the nature of the MECP2 mutations identified in male patients to date and their associated phenotypes.