Background: Mutations in gene are the most common single genetic cause of autism-spectrum disorders, therefore we investigated the possibility that the intermediate alleles may also contribute to the origin of Autistic disorder. Methods: We screened 96 males, recruited from NorthWest of Iran, who were diagnosed with autistic disease for CGG repeat size. Thefrequencies of either intermediate or premutation alleleswerematchedwith 168malecontrols. All patientsandnormalcontrols were of Azeri Turkish ethnicity. Results: Three mutated, five intermediate and four premutation carriers were identified among Autistic patients, compared with one premutation carrier in normal controls, representing a significant excess in small size FMR1 allele carriers (= 0. 006). There was also a significant excess of the intermediate carriers compared with normal controls (= 0. 006). Conclusions: Both of these alleles may show roles in the etiology of autism, possibly as a result of the rise of mRNA. Considering that there are individuals in the general population are carriers of intermediate and premutation alleles, further screening of larger samples of Autism patients is recommended, in order to estimate the role of small size of CGG repeat alleles in the aetiology of autism.

Background. Fragile X-associated premature ovarian insufficiency is clinically defined as a type of early ovarian failure with irregular menstrual cycles, increased follicle-stimulating hormone, premature menopause, and infertility. Genetically, the CGG trinucleotide repeat expansion in the 5'-untranslated region of the FMR1 gene is recognized as a causative factor. The aim of this study was to standardize molecular detection methods and estimate the number of repeats among patients with premature ovarian insufficiency. Methods. After obtaining a consent form and blood sampling, genomic DNA was extracted and treated with sodium bisulfite. The FMR1 gene is located on X chromosome and one allele is methylated by X-inactivation. As a result, the methylation-specific polymerase chain reaction (MS-PCR) was performed using two pairs of specific primers for methylated and non-methylated DNA yelding the products of 108+3n and 168+3n bp, respectively. Following clinical evaluations, 20 sporadic patients and two families with at least two patients were studied. Results. The mean level of follicle-stimulating hormone was 85. 45±, 44. 73UI/L in sporadic and 75. 72±, 33. 61UI/L in familial cases. Ultrasound examinations reported atrophic ovaries in sporadic and familial cases by 80% and 75%, respectively. The evaluation of the trinucleotide repeat expansions on agarose gels showed that two sporadic patients were carriers of FMR1 intermediate alleles (10%). No cases of pre-mutation or full mutation were observed in other sporadic or familial cases and the trinucleotide repeat expansions were estimated between 15 and 35. Conclusion. Due to the role of the FMR1 gene trinucleotide repeat expansion in women with premature ovarian insufficiency, a fast and cost-effective molecular detection method is of particular importance. This test will be beneficial not only in ovarian dysfunction, but also to identify pre-mutations that may expand in next generations leading to fragile X syndrome. Practical Implications. In young women, the detection of expanded CGG trinucleotide repeats in the 5'-untranslated region of the FMR1 gene along with genetic counseling will provide them to plan reproductive life.

Objective: The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between theFMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders ofFMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration (histone acetylation/methylation) of theFMR1 gene in blood and granulosa cells of 20 infertile women.Materials and Methods: In this case-control study, we analyzed the mRNA expression and epigenetic altration of the FMR1gene in blood and granulosa cells of 20 infertile women. These women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of theFMR1 gene was analyzed in all samples.Results: Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with theFMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation (H3K9ac) and di-metylation (H3K9me2) showed significantly higher incorporations in the regulatory regions of theFMR1 gene, including the promoter and the exon 1, whereas tri-metylation (H3K9me3) mark showed no significant difference between two groups.Conclusion: Our data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation ofFMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function.

Introduction: The therapeutic properties of Olibanum have been considered in traditional medicine since ages past. Recent studies indicated the effect of Olibanum on memory enhancement and prevention/treatment of Alzheimer's disease. Fragile X mental retardation protein is the product of the FMR1 gene that mediates memory formation through the development of communications between nerve cells. MAP1B is the FMRP target mRNA and its translation is inhibited by the effect of FMRP. Disturbance in the expression of FMR1 causes fragile X syndrome. Therefore, the aim of this study was to investigate the effect of aqueous extract of Olibanum on the expression of FMR1 and MAP1B genes in hippocampal tissue samples of rats. Materials & Methods: This study was conducted on 18 rats which were divided into groups of control (n=6) and two treatment groups with 75 (n=6) and 150 mg/kg (n=6) concentrations of aqueous extract of Olibanum. The hippocampus of rats was isolated after eight weeks of treatment by Olibanum extract. Total RNA was extracted and cDNA was synthesized in this study. Subsequently, the expression of FMR1 and MAP1B genes was evaluated by a real-time polymerase chain reaction. Ethics code: IR. TBZMED. REC. 1396. 1000 Findings: According to the results, the aqueous extract of Olibanum at a concentration of 75 mg/kg increased the expression of FMR1. In addition, MAP1B gene expression decreased in a dosedependent manner following treatment with Olibanum extract. However, these changes are not statistically significant (P>0. 05). Discussion & Conclusions: The FMRP is a negative translation regulator that mediates synaptic neuronal transmission through inhibition translation of target mRNA, such as MAP1B. Olibanum probably leads to synaptic flexibility and memory improvement through increasing the expression of FMR1 in neuronal cells. This study could pave the way on the use of Olibanum in the treatment of patients with fragile X syndrome in the future.

Alzheimer's disease (AD) is a multifactorial disorder that its progress and development are related to various genetic and environmental factors. The disease onset is affected by both genetic and environmental factors such as oxidative stress, inflammation, and mitochondrial dysfunction, and is remarkably related to age progress. Aluminum, a neurotoxic environmental factor, impairs memory performance and can cause neurodegenerative diseases such as AD. On the other hand, the regulatory RNA-binding product of Fragile X mental retardation (FMR1) gene exerts a translational inhibitory effect on the expression of amyloid precursor protein (APP), the main culprit in AD development. In the present study, we treated AlCl3-induced Alzheimer’ s disease model rats with Frankincense and investigated its protective and therapeutic effects on the AlCl3-induced memory disturbance by behavioral and molecular assays. Also, Rivastigmine was used as a standard control. Morris Water Maze (MWM) was used to assay special memory working of the rats and quantitative real-time PCR (qRT-PCR) was applied to investigate the expression profile of the FMR1 gene in the hippocampus of the treated rats. MWM behavioral tests indicated that both Frankincense and Rivastigmine not only may prevent AlCl3-induced memory impairment but also may alleviate the memory declines induced by AlCl3 in the rats. Expression analysis showed significant upregulation of the FMR1 gene in response to both Frankincense and Rivastigmin treatments. Further, qRT-PCR results revealed that the AlCl3-induced downregulation of the FMR1 gene expression could significantly be reversed by both Frankincense and Rivastigmine, though Rivastigmine was more effective than Frankincense. In conclusion, our results highlighted that Frankincense might be effective both in the prevention and treatment of memory impairments, to some extent, by affecting the FMR1 gene expression.