Gene Reports最新文献

{"title":"Whole exome sequencing based coding variation in nasopharyngeal cancer from tribal population of North-East India","authors":"Sudip Kumar Ghosh ,&nbsp;Raima Das Kundu ,&nbsp;Sankar Kumar Ghosh","doi":"10.1016/j.genrep.2024.102126","DOIUrl":"10.1016/j.genrep.2024.102126","url":null,"abstract":"<div><div>Genome-wide association studies (GWAS) have emerged due to the advent of high-throughput genotyping tools in the study of genetic architecture. Next-generation sequencing techniques, particularly whole exome sequencing (WES) in single nucleotide polymorphism (SNP) analysis, have been used to identify unusual coding variations. Across various demographic groups worldwide, coding differences have varied impacts on the evolution of NPC. However, certain loci related to NPC susceptibility are shared by multiple population types, with the North Eastern (NE) region exhibiting ethnicity-specific cancer variations. In this study, we focused on the major North Eastern tribal populations (Mizoram, Manipur, and Nagaland) to identify NPC-focused germline coding variations through WES. To better understand the genetic association of coding variants with NPC, WES was performed on 15 samples from affected patients and healthy individuals from three different ethnic groups (N = 9 cases and N = 6 controls). Variants were called using the Ion Proton™ platform, and case-control variants were screened for their association studies. All variants were filtered using Haploview, and PLINK software was used to assess the statistical significance of the passed case-control variants. Furthermore, the filtered variants, along with significant variants, were analyzed using different bioinformatics tools and compared with other clinical databases. A total of 60,387 (61.50 %) variations were discovered, of which 578 (p-value ≤0.05) were determined to be significant coding variants. These variants were then processed and filtered using several in silico techniques. The coding regions (exonic) of 10 genes, including <em>CR1</em>, <em>GBP3</em>, <em>QPCT</em>, <em>ADGRV1</em>, <em>ADGB</em>, <em>ALG9</em>, <em>DLAT</em>, <em>CCT6B</em>, <em>GP6</em>, and <em>LRRN4</em>, revealed ten SNPs, all of which are thought to be strongly linked with the NPCs of the three main NER tribes. It is anticipated that protein stability varies as a result of mutation, based on different in silico software such as I-mutant 3.0, MUpro, MutPred, Consurf, Netsurf 3.0, ProtParam tool, and HOPE, where the protein's structural and functional analyses are verified. Nearly all of the 10 nsSNPs exhibit intolerant alterations, indicating their functional significance in crucial areas and potential impact on the stability and function of the corresponding protein. In comparison to the current accepted genetic testing methodology, our work reveals greater sensitivity and specificity for the identification of harmful germline mutations.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102126"},"PeriodicalIF":1.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple discriminant analysis of NR5A1, GATA4, WT1 gene expressions, and their SNPs in poor ovarian response","authors":"Zahra Noormohammadi ,&nbsp;Ashraf Moini ,&nbsp;Elahe Daskar Abkenar ,&nbsp;Aylar Talebi ,&nbsp;Amir Hossein Najafi","doi":"10.1016/j.genrep.2024.102123","DOIUrl":"10.1016/j.genrep.2024.102123","url":null,"abstract":"<div><div>Cumulus cells surrounding the oocyte might be good candidates to explore the possible mechanisms involved in poor ovarian response (POR). In the present study, we investigated if some hub gene expression levels in the pathway of development of oocytes would be associated with the number of oocytes. The genotyping of 15 SNPs of 3′ prime UTR regions of <em>NR5A1</em>, <em>WT1</em>, and <em>GATA4</em> genes in 50 POR and control women blood samples was studied. Gene expression levels were calculated by qPCR in granulosa cells. Among SNPs studied, rs12458 of <em>WT1</em> gene showed significant differences between POR and Non-POR groups (P &lt; 0.05). Linkage disequilibrium analysis showed that rs915034 had significant r statistics with rs961782970 and rs1588613501 of NR5A1 (P &lt; 0.05) as well as rs1253083037 with rs5030320 and rs7008652. Based on Linear discrimination analysis (LDA) significant differences were observed in gene expression levels between POR and non-POR groups (P &gt; 0.05). Principle component analysis (PCA) Adonis revealed distinct differences between individuals of the two groups studied (P = 0.001). We found that some characteristics like age, BMI, and lifestyles such as usage of plastic wares, fast food, frozen food, and stress had significant correlations (P &lt; 0.05) with <em>WT1</em> gene expression level based on Multiple discriminant analysis (MCA) analysis. SNP genotypes of <em>WT1</em> and <em>GATA4 a</em>lso had correlations with <em>WT1</em> gene expression level while only rs12458, rs1062270, rs11785481, and rs57008652 in <em>GATA4</em> gene showed a significant correlation with the down-regulation of <em>WT1</em> gene expression. K means clustering based on protein-protein interaction (PPI) enrichment showed significant interactions (P = 0.00137) which may indicate at least partially biologically connected. The genotypes located at the 3′UTR sequence are associated with the level of gene expressions. <em>WT1</em> gene expression could be used as a potential biomarker for POR women. A further survey is recommended on this pathway.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102123"},"PeriodicalIF":1.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of miR-98-5P and GAB2 gene expression in endometriosis","authors":"Javad Fazeli,&nbsp;Mehran Dehghanian,&nbsp;Ghafour Yarahmadi,&nbsp;Maryam Shirmohamadi,&nbsp;Emad Babakhanzadeh,&nbsp;Mohamadhasan Sheikhha","doi":"10.1016/j.genrep.2024.102121","DOIUrl":"10.1016/j.genrep.2024.102121","url":null,"abstract":"<div><h3>Background</h3><div>GAB2 (Grb2-associated binding protein 2) is a member of the DOS/GAB family of scaffold adaptors that transduce and amplify tyrosine kinase receptor signaling. Recent studies suggest that increased expression of GAB2 promotes tumor progression by enhancing cell proliferation and migration. Studies on the expression of microRNAs have the potential to be useful in the detection, prevention and treatment of various diseases. The anti-cancer effect of Mir-98-5p has been demonstrated in various types of cancer. The aim of this study was to evaluate the gene expression of <em>miR-98-5p</em> and <em>GAB2</em> in individuals with endometriosis compared to the control group.</div></div><div><h3>Materials and methods</h3><div>In this study, eutopic and ectopic samples were taken from 15 women with endometriosis. The control group consisted of samples from 15 women with normal endometrium and no signs of endometriosis. Quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of the <em>miR-98-5p</em> and <em>GAB2</em> genes.</div></div><div><h3>Results</h3><div>We found a remarkable increase in <em>GAB2</em> expression and a significant decrease in <em>miR-98-5p</em> expression in subjects with endometriosis compared to the normal group.</div></div><div><h3>Conclusion</h3><div>Based on the results obtained, it appears that miR-98-5p could serve as a diagnostic and curative biomarker for individuals with endometriosis.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102121"},"PeriodicalIF":1.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"lncRNAs ITFG2-AS1 and MMP25-AS1 have significant high-expression in gastric cancer patients as the potential diagnostic biomarkers: Integrated bioinformatics investigation and validation","authors":"Fatemeh Mohebi ,&nbsp;Zahra Zamanzadeh ,&nbsp;Morteza Abkar ,&nbsp;Mansoureh Azadeh","doi":"10.1016/j.genrep.2024.102107","DOIUrl":"10.1016/j.genrep.2024.102107","url":null,"abstract":"<div><h3>Background</h3><div>The second most frequent cause of cancer-related death is gastric cancer (GC). Recent studies have reported that non-coding RNAs seem to play a crucial role in many tumors. Due to their extraordinary stability, long non-coding RNAs (lncRNAs) have the potential to be employed as biomarkers to identify the presence and prognosis of GC. In this study, we performed an integrated bioinformatics and experimental approach to evaluate the expression and interaction of two novel lncRNAs in the GC samples.</div></div><div><h3>Methods</h3><div>Bioinformatics analyses was performed to demonstrate the lncRNA expression profile of gastric cancer patients. Microarray data analysis was executed by R Studio, using affy and limma packages. Validation of gene expression analysis was carried out by the ENCORI online database. Pathway enrichment analysis was conducted using enrichr and Reactome. Protein interaction analysis was performed by STRING. LncRNA interaction analysis was carried out by lncRRIsearch. RT-qPCR experiment was implemented for validation. Using Receiver operating characteristic (ROC), correlation, and <em>t</em>-tests, the biomarker potential of selected lncRNAs, co-expression of selected lncRNAs, and the differences in the expression level of GC samples have been investigated, based on qRT-PCR experiment.</div></div><div><h3>Results</h3><div>Microarray analysis revealed that ITFG2-AS1 (logFC: 2.25, adj. P. Val: 0.00029) and lncRNA MMP25-AS1 (logFC: 2.25, adj. P. Val: 0.0026) have a significant high-expression in GC samples. RT-qPCR experiments validate the up-regulation of MMP25-AS1 and ITFG2-AS1. Based on the ROC test, ITFG2-AS1 could be a significant diagnostic biomarker of GC (AUC: 0.7225, <em>p</em>-value: 0.0161). ITFG2-AS1 and MMP25-AS1 have a significant co-expression in human GC samples (r: 0.9086, p-value &lt;0.0001). ITFG2-AS1 and MMP25-AS1 regulate the RPGR expression level of RPGR gene. RPGR is a crucial gene in the “Cilium Assembly signaling pathway”. The expression level of ITFG2-AS1 has a non-significant negative correlation with the survival rate of GC patients.</div></div><div><h3>Conclusion</h3><div>ITFG2-AS1 and MMP25-AS1 could be considered as the two potential diagnostic GC biomarkers with significant low expression in tumor samples.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102107"},"PeriodicalIF":1.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into CYP 1A2 dynamics in acute lymphocytic leukemia: Gene regulation, promoter methylation, and pesticide exposure in the Kashmiri population","authors":"Toyeeba Hassan Mir ,&nbsp;Parveena Firdous ,&nbsp;Sajad Geelani ,&nbsp;Aadil Yousuf ,&nbsp;Nadeem Ahmed ,&nbsp;Kamran Nissar ,&nbsp;Abrar Qurashi ,&nbsp;Bashir Ahmad Ganai","doi":"10.1016/j.genrep.2024.102125","DOIUrl":"10.1016/j.genrep.2024.102125","url":null,"abstract":"<div><div>The Cytochrome P450 (CYP) superfamily of proteins occupies a central role in the metabolism, detoxification, and activation of both pharmaceutical compounds and xenobiotics. A well-established association between CYP enzymes and Acute Lymphocytic Leukemia (ALL) underscores their significance in cancer etiology. In light of this, our study is designed to investigate critical facets of the <em>CYP 1A2</em> among ALL patients, including gene expression levels, promoter methylation status, and the presence of pesticide residues. The study cohort encompasses 50 clinically confirmed ALL patients and 30 controls of Kashmiri ethnicity. To discern the epigenetic landscape, we employed bisulfite conversion followed by Methylation-Specific Polymerase Chain Reaction (MSP) to elucidate the promoter methylation profiles of <em>CYP 1A2</em>. Concurrently, we quantified the gene expression levels through quantitative Polymerase Chain Reaction (qPCR). Complementing this, we conducted a comprehensive analysis of pesticide residues obtained from serum employing Gas Chromatography-Mass Spectrometry (GC–MS). The study unveiled a substantial upregulation of the <em>CYP 1A2</em> gene in Acute Lymphocytic Leukemia (ALL) cases, with a remarkable increase by a factor of 22.25 (<em>p</em>-value 0.0081**). Notably, female ALL patients exhibited a significant downregulation of <em>CYP 1A2</em> by 5.45-fold (p-value 0.034*). Furthermore, analysis of <em>CYP 1A2</em> promoters indicated a pronounced hypermethylation pattern in ALL cases. Hyper-methylated females displayed a 2.655-fold higher expression of the gene compared to males (<em>p</em>-value 0.0181*). Subgroup analysis revealed that B-cell type ALL cases exhibited an upregulation of the <em>CYP 1A2</em> gene (<em>p</em>-value 0.0187*). Additionally, a history of pesticide exposure (p-value 0.0119*) and smoking (p-value 0.0094**) were associated with increased <em>CYP 1A2</em> gene expression. Pesticide residue analysis identified the presence of 3,5,6-trichloro-2-pyridinol (TCP), Diethylthiophosphate (DETP), and 2-isopropyl-4-methyl-6-hydroxypyrimidine in ALL samples. In conclusion, our findings underscore the significant upregulation of <em>CYP 1A2</em> in ALL cases, particularly in females, and highlight that promoter hypermethylation appears to enhance, rather than silence, gene expression.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102125"},"PeriodicalIF":1.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA methylation-driven molecular subtypes and immune infiltration in Moyamoya disease","authors":"Yanru Wang ,&nbsp;Cunxin Tan ,&nbsp;Shaoqi Xu ,&nbsp;Junze Zhang ,&nbsp;Zhenyu Zhou ,&nbsp;Yuanli Zhao ,&nbsp;Shihao He ,&nbsp;Ran Duan ,&nbsp;Rong Wang","doi":"10.1016/j.genrep.2024.102124","DOIUrl":"10.1016/j.genrep.2024.102124","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Moyamoya disease (MMD) is a rare cerebrovascular disease with the angiographic characteristic of chronic stenosis of the terminal internal carotid artery and its major branches, which leads to the development of abnormal collateral vessels at the skull base. Previous studies showed that gene mutations alone could not explain the occurrence of MMD, suggesting epigenetic factors involved in MMD pathogenesis. But the role of RNA methylation in MMD has not been studied.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We analyzed four microarray datasets (GSE189993, GSE157628, GSE141024, and GSE141022) from the GEO database, clustering MMD into three molecular subtypes according to RNA methylation-related gene (RMRG) expression profiles. Differential expression analysis and functional enrichment were performed to investigate the molecular mechanisms of MMD. Immune cell infiltration was analyzed, and Spearman correlation assessed the correlation between hub genes and immune cells. Signaling pathways and transcription factor predictions of hub genes were examined, and RNA sequencing (RNA seq) was used to validate findings with MMD STA samples. Finally, we constructed the PTPRM gene knockdown cell model with human brain microvascular endothelial cells (HBMEC) using plasmid transfection and verified the expression of each group with Western blot and polymerase chain reaction (PCR) assays. Then we performed tube formation assays to verify the effects of PTPRM knockdown on angiogenic capacity of HBMECs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our study constructed a novel molecular classification of MMD based on RNA methylation expression and identified totally 15 downregulated genes in MMD compared with controls. The results of with DEGs identified that RNA methylation might affect the pathogenesis progression of MMD. According to this, we constructed molecular subtypes of MMD and selected 5 hub genes as potential biomarkers for MMD (SYPL2, FASTKD2, ZNF543, PTPRM, and TEP1). And immune infiltration analysis indicated that the correlation between the hub genes and immune dysfunction, which could lead to the abnormal migration and proliferation of cells in MMD. PTPRM showed significant positive correlation with RNF213 (Pearson &lt;em&gt;r&lt;/em&gt; = 0.915), while SYPL2 was negatively correlated significantly with GAA (Pearson &lt;em&gt;r&lt;/em&gt; = −0.89). Moreover, we verified the dysregulation of hub genes with RNA seq in MMD STA samples and identified the abnormal expression of PTPRM and SYPL2, which could be potential biomarkers for MMD. We constructed the PTPRM gene knockdown HBMEC model successfully and tube formation assays showed that angiogenic capacity of HBMECs in shRNA-PTPRM group was significantly increased compared with shRNA-NC group.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;RNA methylation appears to play a role in MMD pathogenesis, with immune dysregulation contributing to disease progression. Our study is the first time to explore and verify the ","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102124"},"PeriodicalIF":1.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA Linc00261 sponge's miR-33-regulated PI3-kinase in autism disorder","authors":"Hamidreza Farhadi Rad ,&nbsp;Mahshid Seyed Karimi ,&nbsp;Marjan Behfar ,&nbsp;Ahmad Nazari ,&nbsp;Naeimeh Hassani ,&nbsp;Afshin Hasanvand ,&nbsp;Ali Farhadi","doi":"10.1016/j.genrep.2024.102115","DOIUrl":"10.1016/j.genrep.2024.102115","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication and sensory processing difficulties. Emerging evidence suggests the involvement of long non-coding RNAs (lncRNAs), particularly LIN00261, in its pathogenesis. It has been identified that LIN00261 is differentially expressed in the brains of individuals with ASD and acts as a competing endogenous RNA (ceRNA), “sponging” microRNA-33 (miR-33). This interaction could indirectly influence the PI3-kinase signaling pathway, impacting neuronal maturation and function. Manipulating LIN00261 levels in cellular models of ASD affects PI3-kinase signaling activity, suggesting a potential causal link between LIN00261 and PI3-kinase dysregulation in ASD. Furthermore, investigations have revealed associations between LIN00261 polymorphisms and ASD susceptibility. In conclusion, the lncRNA LIN00261 emerges as a promising candidate gene in ASD, potentially influencing the PI3-kinase signaling pathway through its interaction with miR-33.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102115"},"PeriodicalIF":1.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and treatment in a case of Acrodysostosis1 caused by PRKAR1A gene pathogenic variant","authors":"Ying Xu ,&nbsp;Xiwen Zhang ,&nbsp;Lifen Chen,&nbsp;Lin Li,&nbsp;Junqi Wang,&nbsp;Zhiya Dong","doi":"10.1016/j.genrep.2024.102112","DOIUrl":"10.1016/j.genrep.2024.102112","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to investigate the clinical phenotypic characteristics of acrodysostosis1 (ACRDYS1) caused by <em>PRKAR1A</em> gene mutations, and discuss the correlation between genotype and phenotype by reviewing literatures.</div></div><div><h3>Methods</h3><div>The clinical data of a 13-year-old male child with skeletal dysplasia and multiple hormone resistance was analyzed. The child's clinical exons were examined using second-generation target region capture high-throughput sequencing technology, and suspected mutated loci were verified in the parents through Sanger sequencing. Additionally, a literature review was conducted to analyze the relationship between clinical phenotypes and genotypes in other affected children. The treatment involved growth hormone (GH) for dwarfism and Chorionic Gonadotropin (HCG) for delayed sexual development.</div></div><div><h3>Results</h3><div>The child presented with short stature (≤3SD), low body mass (−1 ∼ -2SD), facial bone abnormalities (wide face, wide eye spacing, maxillary hypoplasia, flattened nasal ridge, small and upturned nostrils), limb hypoplasia (stubby fingers and toes), and delayed puberty (13 years old with 1.5 ml testes and Tanner stage 1). Laboratory tests revealed resistance to parathyroid hormone and thyrotropin, complete growth hormone deficiency, and low testosterone. X-rays indicated skeletal hypoplasia of the extremities. Whole-exome sequencing identified a heterozygous missense mutation (c.524 A &gt; G, p.A346T) in the <em>PRKAR1A</em> gene, which was classified as a pathogenic variant per ACMG. The child's clinical features confirmed ACRDYS1. A literature review showed a link between the <em>PRKAR1A</em> gene and the child's phenotype. The child initially presented with high Thyroid Stimulating Hormone (TSH) and was treated with levothyroxine, adjusted for normal thyroid hormone levels. Despite advanced bone age, severe short stature was addressed with GH therapy (0.16 IU/kg·d), increasing height by 9.6 cm in one year. The child also had small genitalia, treated with HCG, leading to significant enlargement.</div></div><div><h3>Conclusion</h3><div>Clinicians should be attentive to whether children presenting with short stature, short fingers, and facial bone dysplasia also had comorbid hormonal resistance. Genetic testing can confirm the diagnosis of ACRDYS1. Remarkable results have been achieved in terms of height improvement through GH injections and sexual development enhancement through HCG injections. These findings suggested a new direction for studying the pathogenic mechanism of hormone resistance in ACRDYS1 children.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102112"},"PeriodicalIF":1.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Missense variant c.298G > T in the IHH gene: Expanding the phenotypic spectrum of Brachydactyly type A1","authors":"Lin Li ,&nbsp;Haoran Su ,&nbsp;Jiahong Lei ,&nbsp;Yihua Peng ,&nbsp;Yunlin Peng ,&nbsp;Aimin Jia ,&nbsp;Hong Jiang ,&nbsp;Yan Cai","doi":"10.1016/j.genrep.2024.102116","DOIUrl":"10.1016/j.genrep.2024.102116","url":null,"abstract":"<div><div>Brachydactyly type A1 (BDA1) is an autosomal dominant disorder, marked by skeletal abnormalities in the middle and distal phalanges of the digits, a condition first linked to the Indian hedgehog (<em>IHH</em>) gene by Bell in 1951. In this report, we delineate a novel mutation within the <em>IHH</em> gene observed in a Chinese family with consanguineous marriages. The affected individuals exhibit phenotypic traits such as reduced stature and limb length, along with shortened fingers and toes, yet they do not display cognitive impairments. Employing Whole-exome Sequencing (WES), we identified a previously unreported heterozygous mutation, c.298G &gt; T (p.D100Y), located in exon 1 of the <em>IHH</em> gene (NM_002181.3). This mutation was confirmed in the proband and corroborated in other affected relatives through PCR and Sanger sequencing. Subsequent bioinformatics analysis utilizing tools such as MutationTaster, PolyPhen-2, SIFT, and Swissmodel suggests that this variant is likely to be pathogenic. Consequently, we hypothesize that the c.298G &gt; T mutation in the <em>IHH</em> gene may lead to a functional impairment of the IHH protein, thereby inducing the skeletal abnormalities characteristic of BDA1 in the affected members of this family. Future functional studies are warranted to ascertain the pathogenic potential of this mutation.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102116"},"PeriodicalIF":1.0,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A reader IGF2BP3 contributes to gefitinib resistance in lung adenocarcinoma cells by modulating SNAI2 expression","authors":"Risa Takatsuka ,&nbsp;Ryusuke Suzuki ,&nbsp;Minoru Terashima ,&nbsp;Kusuma Suphakhong ,&nbsp;Takahisa Takino ,&nbsp;Shuichi Kawashiri ,&nbsp;Takeshi Suzuki","doi":"10.1016/j.genrep.2024.102113","DOIUrl":"10.1016/j.genrep.2024.102113","url":null,"abstract":"<div><div>Lung adenocarcinoma (LUAD), the predominant subtype of lung cancer, is a major contributor to lung cancer-related mortality, with drug resistance posing a persistent challenge to treatment efficacy. Recent studies suggest that the N6-methyladenosine (m6A) RNA methylation pathway plays a role in the development of acquired drug resistance in LUAD. In this study, we explore the role of the m6A reader IGF2BP3 in resistance to EGFR-TKI, specifically gefitinib. Among various m6A readers, IGF2BP3 is shown to be overexpressed in LUAD, clearly correlating with poor prognosis and advanced disease stages. We find that IGF2BP3 regulates the expression levels and stability of <em>SNAI2</em> mRNA, one of the key transcription factors driving epithelial-mesenchymal transition (EMT), in LUAD cells. We detect the interaction between IGF2BP3 and <em>SNAI2</em> mRNA, which is enhanced through the enzymatic activity of the m6A writer, METTL3. Knockdown of IGF2BP3 reduces the emergence of gefitinib-resistant cells, potentially linked to the decreased SNAI2 expression. Furthermore, berberine treatment reduces IGF2BP3 levels, thereby enhancing gefitinib sensitivity of the cells. Collectively, these results suggest that IGF2BP3 contributes to gefitinib resistance through SNAI2 upregulation, responding to METTL3 enzymatic-activity-dependent binding of IGF2BP3 to <em>SNAI2</em> mRNA. Thus, therapeutically targeting IGF2BP3 may offer a promising strategy to overcome drug resistance in LUAD.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"38 ","pages":"Article 102113"},"PeriodicalIF":1.0,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143134965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}