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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. This study investigated the roles of HOMER1, ATAD1, and miR-361 in AD pathogenesis using microarray (GSE106241, GSE157239; n = 60) and RT-PCR (n = 100; 50 AD patients, 50 controls from Northwest Iran) analyses. Decreased expression of HOMER1 and ATAD1, key regulators of glutamatergic synapses, and miR-361, a potential regulator of both, was observed in AD brain tissue (GSE106241, categorized into seven Braak stages), suggesting a link between their dysregulation, impaired synaptic function, and increased neuroinflammation. However, blood-based RT-PCR showed no significant difference in HOMER1 or ATAD1. miR-361 was significantly lower in AD patients (adjusted p < 0.043). These findings, limited by sample size and lacking a formal power analysis, require further investigation to validate their potential as peripheral biomarkers for AD. Future studies with larger sample sizes are warranted.

Short tandem repeats (STRs) are commonly defined as short runs of repetitive nucleotides, consisting of tandemly repeating 2–6- bp motif units, which are ubiquitously distributed throughout genomes. Functional STRs are polymorphic in the population, and their variations influence gene expression, which subsequently may result in pathogenic phenotypes. To understand STR phenotypic effects and their functional roles, we describe four different mutational mechanisms including the unequal crossing-over model, gene conversion, retrotransposition mechanism and replication slippage. Due to the multi-allelic nature, small length, abundance, high variability, codominant inheritance, nearly neutral evolution, extensive genome coverage and simple assaying of STRs, these markers are widely used in various types of biological research, including population genetics studies, genome mapping, molecular epidemiology, paternity analysis and gene flow studies. In this review, we focus on the current knowledge regarding STR genomic distribution, function, mutation and applications.

Schizophrenia (SCZ) is a severe mental disorder with an unknown etiology. Recent researches indicate that correct myelination and translational regulation play a role in the pathogeny of SCZ. This study evaluated the expression pattern of Ermin (ERMN) and Listerin E3 ubiquitin protein ligase 1 (LTN1) genes, which play a role in myelination and ribosome quality control, respectively. The expression of the ERMN and LTN1 genes in the peripheral blood (PB) of 50 SCZ patients (male/female: 22/28, age (mean ± standard deviation (SD)): 35.9 ± 5.6) and 50 matched healthy controls (male/female: 23/27, age (mean ± SD): 34.7 ± 5.4) were assessed using quantitative polymerase chain reaction. Additionally, we used a bioinformatics approach based on microarray dataset analysis to examine the expression of these two genes in olfactory epithelium (OE) specimens. The expression of ERMN demonstrated no significant differences in PB samples among SCZ patients and healthy controls (adjusted P-value = 0.101). The expression of LTN1 was significantly higher in PB samples obtained from female patients compared with sex-matched controls (posterior beta = 1.734, adjusted P-value < 0.0001). Significant correlations were found between expression of the mentioned genes in PB samples both among SCZ patients and among healthy controls (r = 0.485, P < 0.001 and r = 0.516, P < 0.001, respectively). According to our in silico findings, the ERMN expression levels in OE samples of SCZ were statistically higher than those in controls (log2FC = 1.93, adj.P.Val = 9.66E-15). On the contrary, LTN1 expression levels in OE samples were statistically lower in SCZ cases versus controls (log2FC =  − 0.77, adj.P.Val = 2.14E-06). Besides, a significant correlation was found between the expression of the mentioned genes in OE samples (r =  − 0.60, P < 0.001). In conclusion, the present study is the first evidence to highlight the expression of the ERMN and LTN1 genes in the periphery of SCZ patients. Our findings may provide light on the SCZ’s pathogeny.

Schizophrenia (SCZ) is known as a complicated mental disease with an unknown etiology. The microdeletion of 22q11.2 is the most potent genetic risk factor. Researchers are still trying to find which genes in the deletion region are linked to SCZ. MIR185, encoding microRNA (miR)-185, is present in the minimal 1.5 megabase deletion. Nonetheless, the miR-185 expression profile and its corresponding target genes in animal models and patients with 22q11.2 deletion syndrome (22q11.2DS) imply that more study is required about miR-185 and its corresponding downstream pathways within idiopathic SCZ. The expression of hsa-miR-185-5p and its corresponding target gene, shisa family member 7 (SHISA7), sometimes called CKAMP59, were evaluated in the peripheral blood (PB) samples of Iranian Azeri patients with idiopathic SCZ and healthy subjects, matched by gender and age as control groups by quantitative polymerase chain reaction (qPCR). Fifty SCZ patients (male/female: 22/28, age (mean ± standard deviation (SD)): 35.9 ± 5.6) and 50 matched healthy controls (male/female: 23/27, age (mean ± SD): 34.7 ± 5.4) were enrolled. The expression of hsa-miR-185-5p in the PB samples from subjects with idiopathic SCZ was substantially lower than in that of control groups (posterior beta = -0.985, adjusted P-value < 0.0001). There was also a difference within the expression profile between female and male subgroups (posterior beta = -0.86, adjusted P-value = 0.046 and posterior beta = -1.015, adjusted P-value = 0.004, in turn). Nevertheless, no significant difference was present in the expression level of CKAMP59 between PB samples from patients and control groups (adjusted P-value > 0.999). The analysis of the receiver operating characteristic (ROC) curve suggested that hsa-miR-185-5p may correctly distinguish subjects with idiopathic SCZ from healthy people (the area under curve (AUC) value: 0.722). Furthermore, there was a strong positive correlation between the expression pattern of the abovementioned genes in patients with SCZ and healthy subjects (r = 0.870, P < 0.001 and r = 0.812, P < 0.001, respectively), indicating that this miR works as an enhancer. More research is needed to determine if the hsa-miR-185-5p has an enhancer activity. In summary, this is the first research to highlight the expression of the miR-185 and CKAMP59 genes in the PB from subjects with idiopathic SCZ. Our findings suggest that gene expression alterations mediated by miR-185 may play a role in the pathogenesis of idiopathic and 22q11.2DS SCZ. It is worth noting that, despite a substantial and clear relationship between CKAMP59 and hsa-miR-185-5p, indicating an interactive network, their involvement in the development of SCZ should be reconsidered based on the whole blood sample since the changed expression level of CKAMP59 was not significant. Further research with greater sample sizes and particular leukocyte subsets can greatly make these results stronger.

Alzheimer's disease (AD) is a heterogeneous degenerative disorder of the brain that is on the rise worldwide. One of the critical processes that might be disturbed in AD is gene expression regulation. Tris-tetraprolin (TTP) and ROQUIN are two RNA-binding proteins (RBPs) targeting AU-Rich elements (AREs) and constitutive decay elements (CDEs), respectively. TTP and ROQUIN, members of the CCCH zinc finger protein family, have been demonstrated to fine-tune numerous inflammatory factors. In addition, miR-16 has distinct characteristics and may influence the target mRNA through the ARE site. Interestingly, BDNF mRNA has ARE sites in the 3' untranslated region (UTR) and can be targeted by regulatory factors such as TTP and miR-16 on MRE sequences, forming BDNF/miR-16/TTP regulatory axis. Two microarray datasets were downloaded, including information on mRNAs (GSE106241) and miRNAs (GSE157239) from individuals with AD and corresponding controls. R software was used to identify BDNF, TTP, ROQUIN, and miR-16 expression levels in temporal cortex (TC) tissue datasets. Q-PCR was also used to evaluate the expression of these regulatory factors and the expression of BDNF in the blood of 50 AD and 50 control patients. Bioinformatics evaluation showed that TTP and miR-16 overexpression might act as post-transcriptional regulatory factors to control BDNF expression in AD in TC samples. Instead, this expression pattern was not found in peripheral blood samples from AD patients compared to normal controls. ROQUIN expression was increased in the peripheral blood of AD patients. Hsa-miR-16-5p levels did not show significant differences in peripheral blood samples. Finally, it was shown that TTP and BDNF, based on evaluating the receiver operating characteristic (ROC), effectively identify AD patients from healthy controls. The present study could provide a new perspective on the molecular regulatory processes associated with AD pathogenic mechanisms linked to the BDNF growth factor, although further research is needed on the possible roles of these factors in AD.

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is one of the most common neurodegenerative diseases worldwide. MS results in serious neurological dysfunctions and disability. Disturbances in coding and non-coding genes are key components leading to neurodegeneration along with environmental factors. Long non-coding RNAs (lncRNAs) are long molecules in cells that take part in the regulation of gene expression. Several studies have confirmed the role of lncRNAs in neurodegenerative diseases such as MS. In the current study, we performed a systematic analysis of the role of lncRNAs in this disorder. In total, 53 studies were recognized as eligible for this systematic review. Of the listed lncRNAs, 52 lncRNAs were upregulated, 37 lncRNAs were downregulated, and 11 lncRNAs had no significant expression difference in MS patients compared with controls. We also summarized some of the mechanisms of lncRNA functions in MS. The emerging role of lncRNAs in neurodegenerative diseases suggests that their dysregulation could trigger neuronal death via still unexplored RNA-based regulatory mechanisms. Evaluation of their diagnostic significance and therapeutic potential could help in the design of novel treatments for MS.

Schizophrenia (SCZ) is a severe mental disorder with an unknown pathophysiology. Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been associated with synapse plasticity, learning, and memory, as well as neurodevelopment and neuroprotection. The importance of neurodevelopmental and neurotoxicity-related components in the pathophysiology of SCZ has been highlighted in research on the neurobiology of this disease. The purpose of this research is to investigate the significant expression of two variables, tristetraprolin (TTP) and miR-16, which are known to be regulators of BDNF expression. Fifty Iranian Azeri SCZ patients were enrolled, and fifty healthy volunteers were age- and gender-matched as controls. A quantitative polymerase chain reaction measured the expression levels of the TTP and miR-16 in the peripheral blood (PB) of SCZ patients and healthy people. TTP expression levels in patients were higher than in controls, regardless of gender or age (posterior beta = 1.532, adjusted P -value = 0.012). TTP and miR-16 expression levels were found to be significantly correlated in both SCZ patients and healthy controls ( r  = 0.701, P  < 0.001 and r  = 0.777, P  < 0.001, respectively). Due to the increased expression of TTP in SCZ and the existence of a significant correlation between TTP and miR-16, which helps to act on target mRNAs with AU-rich elements, this mechanism can be considered an influencing factor in SCZ.

DOCK8 immunodeficiency syndrome (DIDS) is a rare autosomal recessive (AR) disorder characterized by elevated serum IgE levels, eosinophilia, recurrent cutaneous infections, severe eczema, and sinopulmonary and gastrointestinal infections. This syndrome is a multisystem disease that is associated with both immune deficiency and neurological complications. In this study, we describe the clinical characteristics of two Iranian patients with DOCK8 deficiency and propose possible mechanisms for this condition. By using whole exome sequencing (WES), we identified two novel mutations, namely c.3233_3234del AG (p.Q1078fs) in exon 6 and a large deletion with 94 kb (c.405–3231 deletion, p.K135fs), in these two patients. These variations are confirmed with Sanger sequencing and CGH array. Subsequent co-segregation analysis is performed to identify inheritance patterns. Both patients were homozygote and their parents were heterozygote for the variations. For further investigation, prediction tools were applied to identify the pathogenicity of the variations and also for modeling the truncated proteins. The patients did not show neurological abnormalities associated with a deficiency of the N terminal region of DOCK8. The absence of neurological complications in the first patient is justifiable due to the maintenance of the proline-rich region in DOCK8, but for the second patient with expanded deletion which is almost like null DOCK8 protein, it is not presumable, pointing to the fact that the C terminal region of the protein might have functions in the proliferation and migration neurons in the peripheral nervous system. Alternatively, it is possible that neurological abnormalities follow an age-dependent pattern, leading to the appearance of related symptoms later in life. Further multiple functional studies are needed to model different identified variants in animal models to confirm our results and suggest possible mechanisms associated with DOCK8 deficiency in this study.

Background FBLN5 -related cutis laxa (CL) is a rare disorder that involves elastic fiber-enriched tissues and is characterized by lax skin and variable systemic involvement such as pulmonary emphysema, arterial involvement, inguinal hernias, hollow viscus diverticula and pyloric stenosis. This type of CL follows mostly autosomal recessive (AR) and less commonly autosomal dominant patterns of inheritance. Results In this study, we detected a novel homozygous missense variant in exon 6 of FBLN5 gene (c.G544C, p.A182P) by using whole exome sequencing in a consanguineous Iranian family with two affected members. Our twin patients showed some of the clinical manifestation of FBLN5-related CL but they did not present pulmonary complications, gastrointestinal and genitourinary abnormalities. The notable thing about this monozygotic twin sisters is that only one of them showed ventricular septal defect, suggesting that this type of CL has intrafamilial variability. Co-segregation analysis showed the patients’ parents and relatives were heterozygous for detected variation suggesting AR form of the CL. In silico prediction tools showed that this mutation is pathogenic and 3D modeling of the normal and mutant protein revealed relative structural alteration of fibulin-5 suggesting that the A182P can contribute to the CL phenotype via the combined effect of lack of protein function and partly misfolding-associated toxicity. Conclusion We underlined the probable roles and functions of the involved domain of fibulin-5 and proposed some possible mechanisms involved in AR form of FBLN5 -related CL. However, further functional studies and subsequent clinical and molecular investigations are needed to confirm our findings.

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that involves social interaction defects, impairment of non-verbal and verbal interactions, and limited interests along with stereotypic activities. Its incidence has been increasing rapidly in recent decades. Despite numerous attempts to understand the pathophysiology of ASD, its exact etiology is still unclear. Recent data shows the role of accurate myelination and translational regulation in ASD’s pathogenesis. In this study, we assessed Ermin ( ERMN ) and Listerin E3 Ubiquitin Protein Ligase 1 ( LTN1 ) genes expression in Iranian ASD patients and age- and gender-matched healthy subjects’ peripheral blood using quantitative real-time PCR to recognize any probable dysregulation in the expression of these genes and propose this disorder’s mechanisms. Analysis of the expression demonstrated a significant ERMN downregulation in total ASD patients compared to the healthy individuals (posterior beta = −0.794, adjusted P -value = 0.025). LTN1 expression was suggestively higher in ASD patients in comparison with the corresponding control individuals. Considering the gender of study participants, the analysis showed that the mentioned genes’ different expression levels were significant only in male subjects. Besides, a significant correlation was found between expression of the mentioned genes ( r = −0.49, P < 0.0001). The present study provides further supports for the contribution of ERMN and LTN1 in ASD’s pathogenesis.