Introduction: Fragile X syndrome (FXS) is one of the most prevalent genetic causes of developmental disability, representing the most frequent form of inherited severe cognitive deficit. The present study was undertaken to investigate FXS and its prevalence in moderate mentally retarded people in patients.Materials and methods: Nineteen people with moderate mental retardation (MR) who were clinically suspicious to have FXS were screened for FXS by using cytogenetic and molecular methods. Blood samples were collected and cultured in specific culture media. G-Banding method was used for karyotyping. To ensure correct results of cytogenetic testing, four suspected case of FXS were tested by PCR. Results were analyzed using logistic regression analysis.Results: Four patients (4%) were found to express fragile X site at q27.3. The results showed that the relationship of FXS with familial, economic status was not significant, but the relationship of FXS with MR and family history was significant.Conclusion: The frequency of FXS positive cases found in this study is similar to other reports of FXS in preselected patients.

Objective Fragile X syndrome (FXS) is the most common cause of inherited mental retardation caused by expansion of a (CGG) repeat region up to 1000 repeat in 5’ region of the FMR1 gene located in FRAXA locus Xq27. 3. To better understand the mechanism involved in expansion of CGG region, the molecular characteristic of the flanking microsatellite markers in the region must be clarify in different populations. We aimed to examine the potential association between specific haplotype and the expanded AC-repeat region in cases and controls chromosomes. Materials & Methods Forty unrelated FXS males and 62 unrelated normal males originating from various regions of Iran were haplotyped by analyzing two CA-repeat markers, FRAXAC1 and DXS548. Results Significant linkage disequilibrium was obtained between DXS548 and FRAXAC1 specific marker alleles and CGG repeat expansion among 40 fragile X cases compared to 62 normal controls. The frequencies of DXS548 and FRAXAC1 longer alleles in patients were significantly higher than that in control group. Two FRAXAC1 long alleles were only observed in cases, possibly due to concatenated mutations. The increase of heterozygosities in fragile X cases (DXS548 78. 6%, FRAXAC1 64. 6%) in comparison to the controls (DXS548 63. 0%, FRAXAC1 47. 0%) showed a multimodal distribution of fragile X associated alleles. Conclusion Haplotype analyses with DXS548 and FRAXAC1 markers represented that haplotype distribution in the normal controls and FXS patients were significantly different, representing a weak founder effect.

Objective: To evidence the need for screening fragile X syndrome (FXS) in egg donors in assisted reproduction protocols. Case report: This is the report of a boy with FXS who inherited the mutated allele from an ovule donated by the mother´, s sister through an assisted reproduction protocol. Identifying premutation (PM) carriers of FXS amongst gamete donors isn’, t part of the obligatory genetic analysis for donors and is only considered by most of the in vitro fertility societies and guidelines as part of the extension screening tests. Conclusion: It is cost-effective to do pre-conceptional screening for the PM or full mutation (FM) of the FMR1 gene affected in FXS in every woman undergoing assisted reproductive methods, including gamete donors even without a positive family history of intellectual disabilities. This case supports the need of rethinking the guidelines on the necessary gamete donor screening tests in assisted reproduction protocols.

Background and Objective: Fragile X syndrome (FXS) is the most common cause of inherited mental retardation. Patients are identified with different levels of mental disabilities, elongated ears, prominent foreheads and chins, enlarged testes, large skull and obesity. This syndrom is generally associated with a break on X chromosome (Xq27.3), which can be observed in cultured chromosomes in specific culture media at metaphase stage. Prevalence rates of FXS in different ethnic groups have been estimated to be about one per 1500 in males and one per 2500 in females. The aim of this study was to determine FXS prevalence in moderate mental retarded students of Zohreh Shamsaei School in Rafsangan city. Materials and Methods: Fifty two students with moderate mental retardation (IQ=55-75) who were clinically suspicious to have FXS were screened for fragile X chromosome by using cytogenetic methods. Blood samples were collected and cultured in specific culture media. G-Banding method was used for karyotyping.Results: Patients consisted of 37 males (71.2%) and 15 females (28.8%) with mean age of 12.7 years (ranged 7-17 years) and mean IQ 65.3) ranged 55-74). 8.1% of male students and 6.6% of female students were found to have fragile X site at Xq27.3 (in total 7.7%). The frequencies of fragile X-positive cells in males and females were 8-52% and 12-27%, respectively. Conclusion: The frequency of fragile X positive cases found in this study is equal to that is reported by other investigators who studied the frequency of fragile X syndrome in preselected patients.      

Background: Fragile X syndrome (FXS) is a genetic disease with intellectual disabilities. FXS is often caused by the CGG-repeat expansion mutation in the FMR1 gene with suppressed FMR1 transcription and decreased protein levels in the brain of the patients. The RNA-guided CRISPR/Cas9 system is a promising targeted ge-nomic editing tool in gene therapy of FXS. In order to evaluate its feasibility, the present study used CRISPR/Cas9 system to target the FMR1 5’,-UTR sites in cultured human neuroblastoma cells. Methods: PCR and DNA clone were used to construct plasmids. CRISPR function was tested by Western blot and flow cytometry. Data were analyzed by a two-tailed unpaired Student’, s t-test using GraphPad software. This research was conducted from 2020 to 2022 in the Second Affiliated Hospital of Soochow University, Suzhou, China. Results: Cell cycle analysis showed significant differences in G1, S and G2/M phases between the two groups (P<0. 05). In the knockout cells, apoptosis was accelerated (P<0. 05) with a significantly down-regulated (P<0. 05) expression of FMRP as compared with the control group. Conclusion: This study provides further understanding about the FMRP function and molecular mechanism of FMR1 gene in nerve cells, and suggests the feasibility of gene therapy in FXS by CRISPR/Cas9 gene editing system.

Dear Editor-in-ChiefThe world prevalence of intellectual disability (ID) has been reported to be 1%-3% of general population and most cases are seen in child/adolescent population (1, 2). The lifetime cost for each person with ID is approximately 1000000 dollars (1). In Iran, ID is mostly seen in adolescents and young people (13/1000) (2). Fragile X syndrome (FXS) is the most common cause of X-linked ID (3). According to Centers for Disease Control and Prevention (CDC) re-port, families became concerned about their children symptoms after first year of life and the diagnosis of FXS will be made a year after (4). Re-

Fragile X syndrome is a genetic condition causing a range of developmental problems, with males more severely affected compared to female patients. The main features include a long and narrow face, large ears, and a prominent jaw and forehead. Males develop enlarged testicles after puberty, and carrier females are expected to show fragile X-associated primary ovarian insufficiency (FXPOI). Fragile X Syndrome (FXS) was suspected in a consanguineous family referred to a Medical Genetics center because of a family history of intellectual disability and primary ovarian insufficiency in their small village population. The cytosine guanine guanine (CGG) repeat expansion of the FMR1 gene in the 65-year-old proband was amplified and then analyzed by Gene Marker software. The female proband showed two expanded alleles, including one full mutation allele and one premutation allele with an accurate size of 74 (CGG) repeats. Despite having two mutant FMR1 alleles and manifesting some symptoms of FXS, she was fertile. Consanguineous marriages and, in more unfavorable conditions, marrying Fragile X-affected or premutation-carrying males with female carriers is not uncommon in such genetically isolated populations. Therefore, the need for Fragile X syndrome examination in suspected patients with similar features and screening their relatives is highly emphasized.

Fragile X syndrome is a genetic condition causing a range of developmental problems, with males more severely affected compared to female patients. The main features include a long and narrow face, large ears, and a prominent jaw and forehead. Males develop enlarged testicles after puberty, and carrier females are expected to show fragile X-associated primary ovarian insufficiency (FXPOI). Fragile X Syndrome (FXS) was suspected in a consanguineous family referred to a Medical Genetics center because of a family history of intellectual disability and primary ovarian insufficiency in their small village population. The cytosine guanine guanine (CGG) repeat expansion of the FMR1 gene in the 65-year-old proband was amplified and then analyzed by Gene Marker software. The female proband showed two expanded alleles, including one full mutation allele and one premutation allele with an accurate size of 74 (CGG) repeats. Despite having two mutant FMR1 alleles and manifesting some symptoms of FXS, she was fertile. Consanguineous marriages and, in more unfavorable conditions, marrying Fragile X-affected or premutation-carrying males with female carriers is not uncommon in such genetically isolated populations. Therefore, the need for Fragile X syndrome examination in suspected patients with similar features and screening their relatives is highly emphasized.