Pub Date : 2024-05-03DOI: 10.1186/s43042-024-00508-3
Sandra Paulina Smieszek
This study aimed to characterize the frequency of RAI1 genetic aberrations associated with Smith–Magenis syndrome (SMS), in a large cohort of autism spectrum disorder (ASD) whole-genome sequencing samples. We aimed to determine the frequencies of RAI1 single-nucleotide variants (SNVs) and copy number variants (CNVs). We report a 2.5 × enrichment of the major deletion and a > 5 × enrichment of the frameshift variants as compared to the known prevalence of SMS 1/15,000. Additionally, we report a significant enrichment of RAI1 rare missense variants in ASD subjects with respect to controls (54 variants/6080 ASD subjects and 6 variants/2541 controls, p-value < 0.002, OR 3.78, CI 1.62–8–81). The SMS phenotype including circadian dysregulation and associated sleep disturbances is mainly caused by RAI1 haploinsufficiency. Sleep disturbances as seen in SMS may overlap in ASD, especially in patients with consequential variants in RAI1 gene.
{"title":"Retinoic Acid-Induced 1 gene variants associated with Smith–Magenis syndrome circadian phenotypes enriched in autism spectrum disorder: whole-genome sequencing study","authors":"Sandra Paulina Smieszek","doi":"10.1186/s43042-024-00508-3","DOIUrl":"https://doi.org/10.1186/s43042-024-00508-3","url":null,"abstract":"This study aimed to characterize the frequency of RAI1 genetic aberrations associated with Smith–Magenis syndrome (SMS), in a large cohort of autism spectrum disorder (ASD) whole-genome sequencing samples. We aimed to determine the frequencies of RAI1 single-nucleotide variants (SNVs) and copy number variants (CNVs). We report a 2.5 × enrichment of the major deletion and a > 5 × enrichment of the frameshift variants as compared to the known prevalence of SMS 1/15,000. Additionally, we report a significant enrichment of RAI1 rare missense variants in ASD subjects with respect to controls (54 variants/6080 ASD subjects and 6 variants/2541 controls, p-value < 0.002, OR 3.78, CI 1.62–8–81). The SMS phenotype including circadian dysregulation and associated sleep disturbances is mainly caused by RAI1 haploinsufficiency. Sleep disturbances as seen in SMS may overlap in ASD, especially in patients with consequential variants in RAI1 gene.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835738","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}
Pub Date : 2024-04-26DOI: 10.1186/s43042-024-00499-1
Dalida El Khatib, Moussa Hojeij, Sandra Sabbagh, Cybel Mehawej, Eliane Chouery, Seung Woo Ryu, JiHye Kim, Andre Mégarbané
Polymicrogyria is a spectrum of complex cortical malformations encompassing multiple subtypes. Of these, bilateral frontoparietal polymicrogyria (BFPP) has been associated with pathogenic variants in the ADGRG1 gene, formerly known as GPR56. BFPP is characterized by cognitive impairment, motor delay, seizures, oculomotor findings, cerebellar, pyramidal signs, and brain malformations that consist of abnormal changes in the cortex, white matter, brainstem, and cerebellum. A large consanguineous Syrian family with five affected individuals exhibiting features of BFPP, is included in this study. These patients presented with cognitive impairment, psychomotor delay, epileptic episodes, cerebellar signs, oculomotor findings, and brain malformations. Through whole exome sequencing, a novel homozygous pathogenic variant in the ADGRG1 gene (NM_201525.4: c.308T > C; p.Leu103Pro) was identified. Here, we report a thorough literature review of cases with BFPP, and we discuss the importance of genetic counseling in families with genetic disorders, especially in underdeveloped countries.
{"title":"ADGRG1-related polymicrogyria syndrome: report on a large consanguineous family with a novel variant and review","authors":"Dalida El Khatib, Moussa Hojeij, Sandra Sabbagh, Cybel Mehawej, Eliane Chouery, Seung Woo Ryu, JiHye Kim, Andre Mégarbané","doi":"10.1186/s43042-024-00499-1","DOIUrl":"https://doi.org/10.1186/s43042-024-00499-1","url":null,"abstract":"Polymicrogyria is a spectrum of complex cortical malformations encompassing multiple subtypes. Of these, bilateral frontoparietal polymicrogyria (BFPP) has been associated with pathogenic variants in the ADGRG1 gene, formerly known as GPR56. BFPP is characterized by cognitive impairment, motor delay, seizures, oculomotor findings, cerebellar, pyramidal signs, and brain malformations that consist of abnormal changes in the cortex, white matter, brainstem, and cerebellum. A large consanguineous Syrian family with five affected individuals exhibiting features of BFPP, is included in this study. These patients presented with cognitive impairment, psychomotor delay, epileptic episodes, cerebellar signs, oculomotor findings, and brain malformations. Through whole exome sequencing, a novel homozygous pathogenic variant in the ADGRG1 gene (NM_201525.4: c.308T > C; p.Leu103Pro) was identified. Here, we report a thorough literature review of cases with BFPP, and we discuss the importance of genetic counseling in families with genetic disorders, especially in underdeveloped countries.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140800585","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}
Pub Date : 2024-04-16DOI: 10.1186/s43042-024-00523-4
Amirul Faez Shamsudin, Sarina Sulong, Imran Ahmad, Nur Salwani Bakar
Statins are well known for their efficacy to improve lipid profiles. Their efficacy varies between individuals and can be modified by patient factors such as genetic polymorphisms. This study used a cross-sectional retrospective design to assess the effect of selected single nucleotide polymorphisms (SNPs) and other patient-specific clinical variables on statin-related lipid profile changes in a subgroup of Malaysians. The impact of low and moderate intensity of statin doses (10–40 mg/day for at least six weeks), regardless of statin types, was assessed between SNPs of previously identified genes with clinical relation to statin efficacy and lipid profile changes before (baseline) and after statin treatment; two ranges of treatment durations, i.e. ≤ 6 months and 7–12 months. DNA was extracted from patient's venous blood (3 mL), and SNP genotyping was performed using PCR–RFLP method. Using a dominant genetic model, the association between selected SNPs from six genes of interest (ABCG2, ABCC2, APOE, APOA5, GATM and COQ2) and the patients' lipid profiles was investigated. A total of 229 statin-treated patients were included. The mean age of the patients was 53 ± 7.16 years, and they were mostly females (53.3%), Malay (96.1%), and were taking atorvastatin and simvastatin (90.4%). Seven SNPs genotyped from six genes investigated were related to different lipid profile before and after statin treatment. At baseline, ABCG2 rs2231142 (P = 0.035) and APOA5 rs662799 (P = 0.007) variants had higher HDL-c levels, while ABCC2 rs717620 variants had higher TC (P = 0.040) and LDL-c levels (P = 0.022). Following statin treatment, ABCC2 rs717620 (lower TG, P = 0.009) and APOA5 rs662799 (higher HDL, P = 0.031; lower TG, P = 0.037) were associated with improved lipid profiles, with the association being substantially related to males carrying minor alleles of the SNPs. None of the investigated SNPs were related to significant statin-related LDL-c lowering effects during statin therapy. To better understand inter-individual heterogeneity in lipid profiles during statin therapy, it would be helpful to take patient genetics and gender into consideration before and after administering statins.
{"title":"Association between genetic polymorphisms and other attributing factors with lipid profiles among statin users: a cross-sectional retrospective study","authors":"Amirul Faez Shamsudin, Sarina Sulong, Imran Ahmad, Nur Salwani Bakar","doi":"10.1186/s43042-024-00523-4","DOIUrl":"https://doi.org/10.1186/s43042-024-00523-4","url":null,"abstract":"Statins are well known for their efficacy to improve lipid profiles. Their efficacy varies between individuals and can be modified by patient factors such as genetic polymorphisms. This study used a cross-sectional retrospective design to assess the effect of selected single nucleotide polymorphisms (SNPs) and other patient-specific clinical variables on statin-related lipid profile changes in a subgroup of Malaysians. The impact of low and moderate intensity of statin doses (10–40 mg/day for at least six weeks), regardless of statin types, was assessed between SNPs of previously identified genes with clinical relation to statin efficacy and lipid profile changes before (baseline) and after statin treatment; two ranges of treatment durations, i.e. ≤ 6 months and 7–12 months. DNA was extracted from patient's venous blood (3 mL), and SNP genotyping was performed using PCR–RFLP method. Using a dominant genetic model, the association between selected SNPs from six genes of interest (ABCG2, ABCC2, APOE, APOA5, GATM and COQ2) and the patients' lipid profiles was investigated. A total of 229 statin-treated patients were included. The mean age of the patients was 53 ± 7.16 years, and they were mostly females (53.3%), Malay (96.1%), and were taking atorvastatin and simvastatin (90.4%). Seven SNPs genotyped from six genes investigated were related to different lipid profile before and after statin treatment. At baseline, ABCG2 rs2231142 (P = 0.035) and APOA5 rs662799 (P = 0.007) variants had higher HDL-c levels, while ABCC2 rs717620 variants had higher TC (P = 0.040) and LDL-c levels (P = 0.022). Following statin treatment, ABCC2 rs717620 (lower TG, P = 0.009) and APOA5 rs662799 (higher HDL, P = 0.031; lower TG, P = 0.037) were associated with improved lipid profiles, with the association being substantially related to males carrying minor alleles of the SNPs. None of the investigated SNPs were related to significant statin-related LDL-c lowering effects during statin therapy. To better understand inter-individual heterogeneity in lipid profiles during statin therapy, it would be helpful to take patient genetics and gender into consideration before and after administering statins.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612897","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}
The CXCR4 chemokine receptor is a G protein-coupled receptor that plays a role in many physiological processes and diseases, such as cancer metastasis, HIV infection, and immune response. Because of this, it may be possible to target it therapeutically. In addition, the active ingredient of Phaseolus vulgaris L (PVL) has been reported to have anti-inflammatory, antioxidant, and anticancer properties. Novel CXCR4 antagonists from natural resources can be a promising drug development product using a computational approach. This study aims to explore the active compound in PVL that has the responsibility to inhibit CXCR4 using molecular docking and dynamics simulation. Pharmacokinetic analysis were performed using the pkCSM, OSIRIS for toxicity risk analysis, and the PerMM for membrane permeability assessment. Molecular docking was performed using PyRx software to determine the interaction between the CXCR4 target protein from the PDB database and the active component of PVL from the PubChem database. A molecular dynamics (MD) simulation was performed to determine the stability of the interaction using the WEBGRO Macromolecular Simulations online server. The analysis were performed by comparing the results with plerixafor as a control ligand. The pharmacokinetic analysis of quercetin, kaempferol, myricetin, catechin, 3,4-dihydroxybenzoic acid, and daidzin in PVL showed that they met the drug-like criteria. These chemicals were expected to have medium-risk effects on mutagenesis and tumorigenesis, with the exception of catechin, which has no risk of toxicity, and daidzin, which has high-risk effects on mutagenesis and reproduction. Molecular docking identified that quercetin (− 6.6 kcal/mol), myricetin (− 6.6 kcal/mol), catechin (− 6.5 kcal/mol), and 3,4-dihydroxybenzoic acid (− 5.4 kcal/mol) bind to CXCR4 with the highest affinity compared to plerixafor (− 5.0 kcal/mol) and can bind to the same binding pocket with key residues Asp187, Asp97, and Glu288. The MD simulation analysis showed that quercetin has a similar stability interaction compared to the control. Considering the pharmacokinetic analysis, molecular docking, and MD simulations, quercetin, myricetin, and 3,4-dihydroxybenzoic acid have the potential to become CXCR4 agonists with their good oral bioavailability and safety properties for the novel drug candidates. Future studies are needed to consider the molecular docking result.
{"title":"Exploring the potential of phytoconstituents from Phaseolus vulgaris L against C-X-C motif chemokine receptor 4 (CXCR4): a bioinformatic and molecular dynamic simulations approach","authors":"Cesarius Singgih Wahono, Mokhamad Fahmi Rizki Syaban, Mirza Zaka Pratama, Perdana Aditya Rahman, Nabila Erina Erwan","doi":"10.1186/s43042-024-00510-9","DOIUrl":"https://doi.org/10.1186/s43042-024-00510-9","url":null,"abstract":"The CXCR4 chemokine receptor is a G protein-coupled receptor that plays a role in many physiological processes and diseases, such as cancer metastasis, HIV infection, and immune response. Because of this, it may be possible to target it therapeutically. In addition, the active ingredient of Phaseolus vulgaris L (PVL) has been reported to have anti-inflammatory, antioxidant, and anticancer properties. Novel CXCR4 antagonists from natural resources can be a promising drug development product using a computational approach. This study aims to explore the active compound in PVL that has the responsibility to inhibit CXCR4 using molecular docking and dynamics simulation. Pharmacokinetic analysis were performed using the pkCSM, OSIRIS for toxicity risk analysis, and the PerMM for membrane permeability assessment. Molecular docking was performed using PyRx software to determine the interaction between the CXCR4 target protein from the PDB database and the active component of PVL from the PubChem database. A molecular dynamics (MD) simulation was performed to determine the stability of the interaction using the WEBGRO Macromolecular Simulations online server. The analysis were performed by comparing the results with plerixafor as a control ligand. The pharmacokinetic analysis of quercetin, kaempferol, myricetin, catechin, 3,4-dihydroxybenzoic acid, and daidzin in PVL showed that they met the drug-like criteria. These chemicals were expected to have medium-risk effects on mutagenesis and tumorigenesis, with the exception of catechin, which has no risk of toxicity, and daidzin, which has high-risk effects on mutagenesis and reproduction. Molecular docking identified that quercetin (− 6.6 kcal/mol), myricetin (− 6.6 kcal/mol), catechin (− 6.5 kcal/mol), and 3,4-dihydroxybenzoic acid (− 5.4 kcal/mol) bind to CXCR4 with the highest affinity compared to plerixafor (− 5.0 kcal/mol) and can bind to the same binding pocket with key residues Asp187, Asp97, and Glu288. The MD simulation analysis showed that quercetin has a similar stability interaction compared to the control. Considering the pharmacokinetic analysis, molecular docking, and MD simulations, quercetin, myricetin, and 3,4-dihydroxybenzoic acid have the potential to become CXCR4 agonists with their good oral bioavailability and safety properties for the novel drug candidates. Future studies are needed to consider the molecular docking result.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594114","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}
Pub Date : 2024-04-09DOI: 10.1186/s43042-024-00525-2
Tuğba Semerci Sevimli, Murat Sevimli, Ayşe Esra Manguoğlu, Güven Lüleci
It is known that BRCA1 and BRCA2 genes’ mutation carriers are predisposed to breast and ovarian cancers and other organ cancers such as prostate, colon and cervix. In the previous study performed at X University, all coding exons of both genes were screened by denaturing gradient gel electrophoresis (DGGE). In addition to various nonsense, missense mutations, polymorphisms and intronic region changes, seven novel missense mutations, including H513L, H816P and S1517Y in BRCA1 and S326R, G258P, E2903K and N2742S in BRCA2, had been identified. To determine whether these unclassified variants are pathogenic, DNA samples of 150 healthy individuals without a known cancer history in the family were screened in this study for these seven novel missense mutations. These DNA samples were recruited from archives of previous polymorphism studies. PCR performed DNA amplifications, and denaturing high-performance liquid chromatography (DHPLC) techniques did mutation screenings. Peak patterns suggestive of a change in DNA fragments were considered for sequencing analyses. Analyses revealed that none of the 150 DNA samples had any change in the seven screened fragments. As a result, it is assumed that these seven mutations might be novel pathogenic mutations described in the Turkish population. In conclusion, these carriers must be informed about the mutation and given appropriate genetic counseling by their physicians. In addition, genetic testing must be offered to high-risk individuals (men/women) in the family so that it would be possible for other family members to have genetic counseling and contribute to disease prevention. On the other hand, these findings would contribute to current literature with novel results and shed light on future research.
众所周知，BRCA1 和 BRCA2 基因突变携带者易患乳腺癌、卵巢癌和其他器官癌症，如前列腺癌、结肠癌和宫颈癌。在 X 大学之前进行的研究中，通过变性梯度凝胶电泳（DGGE）筛选了这两个基因的所有编码外显子。除了各种无义突变、错义突变、多态性和内含子区变化外，还发现了七种新型错义突变，包括 BRCA1 中的 H513L、H816P 和 S1517Y，以及 BRCA2 中的 S326R、G258P、E2903K 和 N2742S。为了确定这些未分类的变异是否具有致病性，本研究对 150 个没有已知家族癌症病史的健康人的 DNA 样本进行了筛查，以检测这 7 个新型错义突变。这些 DNA 样本是从以前的多态性研究档案中收集的。聚合酶链式反应（PCR）进行 DNA 扩增，变性高效液相色谱（DHPLC）技术进行突变筛选。对提示 DNA 片段发生变化的峰值模式进行测序分析。分析表明，在 150 份 DNA 样本中，7 个筛选出的片段均未发生任何变化。因此，推测这七种突变可能是土耳其人群中出现的新型致病突变。总之，医生必须告知这些基因突变携带者，并为他们提供适当的遗传咨询。此外，还必须为家族中的高危个体（男性/女性）提供基因检测，以便其他家庭成员也能接受基因咨询，为疾病预防做出贡献。另一方面，这些研究结果将为目前的文献提供新的成果，并为未来的研究提供启示。
{"title":"Turkish population-based screening for first identified changes of BRCA1 and BRCA2 genes in breast and/or ovarian cancer patients","authors":"Tuğba Semerci Sevimli, Murat Sevimli, Ayşe Esra Manguoğlu, Güven Lüleci","doi":"10.1186/s43042-024-00525-2","DOIUrl":"https://doi.org/10.1186/s43042-024-00525-2","url":null,"abstract":"It is known that BRCA1 and BRCA2 genes’ mutation carriers are predisposed to breast and ovarian cancers and other organ cancers such as prostate, colon and cervix. In the previous study performed at X University, all coding exons of both genes were screened by denaturing gradient gel electrophoresis (DGGE). In addition to various nonsense, missense mutations, polymorphisms and intronic region changes, seven novel missense mutations, including H513L, H816P and S1517Y in BRCA1 and S326R, G258P, E2903K and N2742S in BRCA2, had been identified. To determine whether these unclassified variants are pathogenic, DNA samples of 150 healthy individuals without a known cancer history in the family were screened in this study for these seven novel missense mutations. These DNA samples were recruited from archives of previous polymorphism studies. PCR performed DNA amplifications, and denaturing high-performance liquid chromatography (DHPLC) techniques did mutation screenings. Peak patterns suggestive of a change in DNA fragments were considered for sequencing analyses. Analyses revealed that none of the 150 DNA samples had any change in the seven screened fragments. As a result, it is assumed that these seven mutations might be novel pathogenic mutations described in the Turkish population. In conclusion, these carriers must be informed about the mutation and given appropriate genetic counseling by their physicians. In addition, genetic testing must be offered to high-risk individuals (men/women) in the family so that it would be possible for other family members to have genetic counseling and contribute to disease prevention. On the other hand, these findings would contribute to current literature with novel results and shed light on future research.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594063","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}
Pub Date : 2024-04-09DOI: 10.1186/s43042-024-00522-5
S. P. Angelin Claret, Jose Prakash Dharmian, A. Muthu Manokar
Artificial intelligence (AI) has shown great promise in the field of healthcare as a means of improving the diagnosis of skin cancer. The objective of this research is to enhance the precision and effectiveness of skin cancer identification by the incorporation of convolutional neural networks (CNNs) and discrete wavelet transformation (DWT). Making use of AI-driven techniques has the potential to completely transform the diagnosis process by providing quicker and more accurate evaluations of skin lesions. In an effort to improve dermatology and give physicians reliable resources for early and precise skin cancer diagnosis, this work explores the combination of CNNs with DWT. The accurate and timely classification of skin cancer lesions plays a crucial role in early diagnosis and effective treatment. In this, we propose a novel approach for skin cancer classification using discrete wavelet transformation (DWT). The DWT is employed to extract relevant features from skin lesion images, which are then used to train a classification model. The effectiveness of the suggested approach is assessed through the examination of a dataset of skin lesion images with known classes (malignant or benign). The outcomes of the experiment demonstrate that the suggested model successfully attained a classification result of sensitivity as 94% and specificity as 91% when compared with artificial neural network (ANN) and multilayer perceptron methods. The HAM 10000 dataset is employed to explore and evaluate the effectiveness of the proposed model, leading to improved accuracy compared to the existing machine learning algorithms in utilization. The results demonstrate the effectiveness of the DWT-based approach in accurately classifying skin cancer lesions, thus aiding in early detection and diagnosis.
{"title":"Artificial intelligence-driven enhanced skin cancer diagnosis: leveraging convolutional neural networks with discrete wavelet transformation","authors":"S. P. Angelin Claret, Jose Prakash Dharmian, A. Muthu Manokar","doi":"10.1186/s43042-024-00522-5","DOIUrl":"https://doi.org/10.1186/s43042-024-00522-5","url":null,"abstract":"Artificial intelligence (AI) has shown great promise in the field of healthcare as a means of improving the diagnosis of skin cancer. The objective of this research is to enhance the precision and effectiveness of skin cancer identification by the incorporation of convolutional neural networks (CNNs) and discrete wavelet transformation (DWT). Making use of AI-driven techniques has the potential to completely transform the diagnosis process by providing quicker and more accurate evaluations of skin lesions. In an effort to improve dermatology and give physicians reliable resources for early and precise skin cancer diagnosis, this work explores the combination of CNNs with DWT. The accurate and timely classification of skin cancer lesions plays a crucial role in early diagnosis and effective treatment. In this, we propose a novel approach for skin cancer classification using discrete wavelet transformation (DWT). The DWT is employed to extract relevant features from skin lesion images, which are then used to train a classification model. The effectiveness of the suggested approach is assessed through the examination of a dataset of skin lesion images with known classes (malignant or benign). The outcomes of the experiment demonstrate that the suggested model successfully attained a classification result of sensitivity as 94% and specificity as 91% when compared with artificial neural network (ANN) and multilayer perceptron methods. The HAM 10000 dataset is employed to explore and evaluate the effectiveness of the proposed model, leading to improved accuracy compared to the existing machine learning algorithms in utilization. The results demonstrate the effectiveness of the DWT-based approach in accurately classifying skin cancer lesions, thus aiding in early detection and diagnosis.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594086","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}
Pub Date : 2024-04-08DOI: 10.1186/s43042-024-00520-7
Lili Yang, Yueming Ding
The link between anxiety and tinnitus severity has garnered significant scholarly interest, with numerous studies identifying a positive correlation. Despite this, the genetic basis of this relationship remains underexplored. Leveraging publicly accessible GWAS data, this study employs Mendelian randomization to elucidate the genetic causality between anxiety and tinnitus severity. This research analyzed single nucleotide polymorphisms (SNPs) related to anxiety and tinnitus severity from the UK Biobank, utilizing aggregated data from genome-wide association studies (GWAS). Instrumental variables linked to anxiety were meticulously selected. The study implemented several Mendelian randomization techniques, including “mr_ivw,” “mr_egger_regression,” “mr_weighted_median,” “mr_simple_mode,” and “mr_weighted_mode,” to assess the causal impact of anxiety on tinnitus risk through odds ratios (ORs). Sensitivity analyses, including MR-Egger and the leave-one-out method, were conducted to ensure result stability. The F-value was also calculated to ascertain the strength of the instrumental variables. Analysis identified five SNPs as instrumental variables. The calculated ORs and 95% confidence intervals from MR-Egger regression, weighted median, and inverse variance weighting showed no statistically significant causal relationship between anxiety and severe tinnitus, with all P-values exceeding 0.05. This lack of statistical significance, consistent across various methods, indicates no genetic causality between anxiety and tinnitus severity. Furthermore, no evidence of heterogeneity (P = 0.80) or horizontal pleiotropy (P = 0.31) was found, reinforcing the robustness of the instrumental variables (F > 10). Our Mendelian randomization analysis reveals no genetic causality between anxiety and tinnitus severity, suggesting the need for further research into the multifaceted etiology of tinnitus.
焦虑与耳鸣严重程度之间的关系引起了学者们的极大兴趣，许多研究都发现两者之间存在正相关关系。尽管如此，这种关系的遗传基础仍未得到充分探索。本研究利用公开的 GWAS 数据，采用孟德尔随机法来阐明焦虑与耳鸣严重程度之间的遗传因果关系。本研究利用全基因组关联研究（GWAS）的汇总数据，分析了英国生物库中与焦虑和耳鸣严重程度相关的单核苷酸多态性（SNPs）。与焦虑相关的工具变量均经过精心筛选。研究采用了多种孟德尔随机化技术，包括 "mr_ivw"、"mr_egger_regression"、"mr_weighted_median"、"mr_simple_mode "和 "mr_weighted_mode"，通过几率比（ORs）评估焦虑对耳鸣风险的因果影响。为确保结果的稳定性，还进行了敏感性分析，包括 MR-Egger 分析和撇除法分析。还计算了 F 值，以确定工具变量的强度。分析确定了五个 SNP 为工具变量。通过MR-Egger回归、加权中位数和反方差加权计算得出的ORs和95%置信区间显示，焦虑与严重耳鸣之间没有统计学意义上的因果关系，所有P值均超过0.05。在各种方法中均无统计学意义，这表明焦虑与耳鸣严重程度之间不存在遗传因果关系。此外，没有发现异质性（P = 0.80）或水平多效性（P = 0.31）的证据，这加强了工具变量（F > 10）的稳健性。我们的孟德尔随机分析表明，焦虑与耳鸣严重程度之间没有遗传因果关系，这表明有必要进一步研究耳鸣的多方面病因。
{"title":"The causal relationship between anxiety and tinnitus severity: a Mendelian randomization study","authors":"Lili Yang, Yueming Ding","doi":"10.1186/s43042-024-00520-7","DOIUrl":"https://doi.org/10.1186/s43042-024-00520-7","url":null,"abstract":"The link between anxiety and tinnitus severity has garnered significant scholarly interest, with numerous studies identifying a positive correlation. Despite this, the genetic basis of this relationship remains underexplored. Leveraging publicly accessible GWAS data, this study employs Mendelian randomization to elucidate the genetic causality between anxiety and tinnitus severity. This research analyzed single nucleotide polymorphisms (SNPs) related to anxiety and tinnitus severity from the UK Biobank, utilizing aggregated data from genome-wide association studies (GWAS). Instrumental variables linked to anxiety were meticulously selected. The study implemented several Mendelian randomization techniques, including “mr_ivw,” “mr_egger_regression,” “mr_weighted_median,” “mr_simple_mode,” and “mr_weighted_mode,” to assess the causal impact of anxiety on tinnitus risk through odds ratios (ORs). Sensitivity analyses, including MR-Egger and the leave-one-out method, were conducted to ensure result stability. The F-value was also calculated to ascertain the strength of the instrumental variables. Analysis identified five SNPs as instrumental variables. The calculated ORs and 95% confidence intervals from MR-Egger regression, weighted median, and inverse variance weighting showed no statistically significant causal relationship between anxiety and severe tinnitus, with all P-values exceeding 0.05. This lack of statistical significance, consistent across various methods, indicates no genetic causality between anxiety and tinnitus severity. Furthermore, no evidence of heterogeneity (P = 0.80) or horizontal pleiotropy (P = 0.31) was found, reinforcing the robustness of the instrumental variables (F > 10). Our Mendelian randomization analysis reveals no genetic causality between anxiety and tinnitus severity, suggesting the need for further research into the multifaceted etiology of tinnitus. ","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594052","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}
Pub Date : 2024-04-08DOI: 10.1186/s43042-024-00524-3
Sara A. Nusair, Gehan Galal, Sara M. Radwan
Hepatocellular carcinoma (HCC) is a severe threat and a main reason for cancer-related deaths around the world. Drug resistance to sorafenib (Sorf), the effective HCC first-line therapy, is very common. A number of natural compounds, notably bee venom (BV), have been claimed to show a great impact against cancer when administered on its own or in conjunction with chemotherapy. Thus, this study aimed to investigate the anticancer effect of BV alone and/or combined with Sorf on HepG2 liver cancer cell lines. Both mRNA and protein expressions of Bax, Bcl-2 and Beclin-1 were investigated by quantitative real-time PCR (qPCR) and western blot respectively, to examine the apoptotic and autophagic regulatory effects of BV and Sorf single treatments plus BV/Sorf combination on HepG2 cell lines. Our findings showed that BV and Sorf had considerable dose-dependent anti-proliferative effects on HepG2 cells whether administered alone or in combination, with the greatest impact for the combined therapies. Single BV and Sorf treatments showed IC50 of 93.21 and 7.28 μg/ml respectively, while combined treatment showed IC50 of 6.73 μg/ml BV + 6.73 μg/ml Sorf. Moreover, both the pro-apoptotic gene Bax and the autophagy-related gene Beclin-1 showed significant up-regulation in their mRNA expression, while the anti-apoptotic Bcl-2 mRNA gene expression showed significant down-regulation after BV/Sorf treatment as compared to either BV or Sorf single treatment. These qPCR results were further confirmed by western blot. These findings indicate that BV synergistically potentiates the anticancer effect of Sorf on HepG2 cells through induction of apoptotic and autophagic machineries.
{"title":"The potential anticancer effect of bee venom in combination with sorafenib against HepG2 cell lines via induction of apoptosis and autophagy candidate genes","authors":"Sara A. Nusair, Gehan Galal, Sara M. Radwan","doi":"10.1186/s43042-024-00524-3","DOIUrl":"https://doi.org/10.1186/s43042-024-00524-3","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a severe threat and a main reason for cancer-related deaths around the world. Drug resistance to sorafenib (Sorf), the effective HCC first-line therapy, is very common. A number of natural compounds, notably bee venom (BV), have been claimed to show a great impact against cancer when administered on its own or in conjunction with chemotherapy. Thus, this study aimed to investigate the anticancer effect of BV alone and/or combined with Sorf on HepG2 liver cancer cell lines. Both mRNA and protein expressions of Bax, Bcl-2 and Beclin-1 were investigated by quantitative real-time PCR (qPCR) and western blot respectively, to examine the apoptotic and autophagic regulatory effects of BV and Sorf single treatments plus BV/Sorf combination on HepG2 cell lines. Our findings showed that BV and Sorf had considerable dose-dependent anti-proliferative effects on HepG2 cells whether administered alone or in combination, with the greatest impact for the combined therapies. Single BV and Sorf treatments showed IC50 of 93.21 and 7.28 μg/ml respectively, while combined treatment showed IC50 of 6.73 μg/ml BV + 6.73 μg/ml Sorf. Moreover, both the pro-apoptotic gene Bax and the autophagy-related gene Beclin-1 showed significant up-regulation in their mRNA expression, while the anti-apoptotic Bcl-2 mRNA gene expression showed significant down-regulation after BV/Sorf treatment as compared to either BV or Sorf single treatment. These qPCR results were further confirmed by western blot. These findings indicate that BV synergistically potentiates the anticancer effect of Sorf on HepG2 cells through induction of apoptotic and autophagic machineries.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593920","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}
Pub Date : 2024-04-05DOI: 10.1186/s43042-024-00521-6
Zahraa Isam Jameel
Colorectal cancer (CRC) is a major cause to global cancer-related mortality. The development of colorectal cancer is linked to hereditary variables that exhibit variability. The objective of this investigation was to assess the potential correlation between microRNA gene polymorphisms and colorectal cancer (CRC) throughout the Iraqi population. DNA samples were obtained from a cohort of 100 individuals diagnosed with the (CRC) disease, as well as 100 samples as control group. Four primers were designed to amplify four specific high-frequency variants found within microRNA molecules. These variants include Mir146a GC, Mir423 AC, Mir196a2, and Mir370. The genotyping of the PCR fragments was performed using the single-strand conformation polymorphism (SSCP) method, followed by direct sequencing of each genotype. Genotyping experiments confirmed the variability of four targeted variants, namely Mir146a GC, Mir 423 AC, Mir196a2, and Mir370 tend to exhibit a significant association with (CRC). Individuals with Mir146a: GC and Mir 423 AC genotype showed a possible association with the increased risk of (CRC), respectively (P = 0.001; OD 0.50; CI 95% 0.33–0.76; P = 0.002; OD 0.53; CI 95% 0.36–0.80). Individuals with Mir196a2: TT and Mir370 GG genotype exhibited a potential association with (CRC) (P = 0.017; OD 0.44; CI 95% 0.22–0.86; P ≤ 0.001; OD 0.24; CI 95% 0.11–0.50). The study reveals that single nucleotide polymorphisms (SNPs) in microRNA have a notable and distinct correlation with the heightened susceptibility to colorectal cancer (CRC).
结直肠癌（CRC）是全球癌症相关死亡率的主要原因。结直肠癌的发生与遗传变量有关，而遗传变量又具有变异性。这项调查的目的是评估伊拉克人口中 microRNA 基因多态性与结直肠癌（CRC）之间的潜在相关性。研究人员从 100 名被诊断患有（CRC）疾病的患者以及 100 名对照组样本中获取了 DNA 样本。设计了四种引物来扩增 microRNA 分子中的四种特定高频变异。这些变异包括 Mir146a GC, Mir423 AC, Mir196a2 和 Mir370。利用单链构象多态性（SSCP）方法对 PCR 片段进行基因分型，然后对每个基因型进行直接测序。基因分型实验证实了 Mir146a GC 、Mir 423 AC 、Mir196a2 和 Mir370 这四个目标变异体的变异性往往与癌症（CRC）有显著的关联。Mir146a：GC和Mir 423 AC 基因型分别显示与（CRC）风险增加可能有关（P = 0.001; OD 0.50; CI 95% 0.33-0.76；P = 0.002; OD 0.53; CI 95% 0.36-0.80）。具有 Mir196a2: TT 和 Mir370 GG 基因型的个体与（CRC）有潜在关联（P = 0.017; OD 0.44; CI 95% 0.22-0.86; P ≤ 0.001; OD 0.24; CI 95% 0.11-0.50）。该研究揭示了微RNA的单核苷酸多态性（SNPs）与结直肠癌（CRC）易感性的升高有着显著而明显的相关性。
{"title":"Four microRNA gene polymorphisms are associated with Iraqi patients with colorectal cancer","authors":"Zahraa Isam Jameel","doi":"10.1186/s43042-024-00521-6","DOIUrl":"https://doi.org/10.1186/s43042-024-00521-6","url":null,"abstract":"Colorectal cancer (CRC) is a major cause to global cancer-related mortality. The development of colorectal cancer is linked to hereditary variables that exhibit variability. The objective of this investigation was to assess the potential correlation between microRNA gene polymorphisms and colorectal cancer (CRC) throughout the Iraqi population. DNA samples were obtained from a cohort of 100 individuals diagnosed with the (CRC) disease, as well as 100 samples as control group. Four primers were designed to amplify four specific high-frequency variants found within microRNA molecules. These variants include Mir146a GC, Mir423 AC, Mir196a2, and Mir370. The genotyping of the PCR fragments was performed using the single-strand conformation polymorphism (SSCP) method, followed by direct sequencing of each genotype. Genotyping experiments confirmed the variability of four targeted variants, namely Mir146a GC, Mir 423 AC, Mir196a2, and Mir370 tend to exhibit a significant association with (CRC). Individuals with Mir146a: GC and Mir 423 AC genotype showed a possible association with the increased risk of (CRC), respectively (P = 0.001; OD 0.50; CI 95% 0.33–0.76; P = 0.002; OD 0.53; CI 95% 0.36–0.80). Individuals with Mir196a2: TT and Mir370 GG genotype exhibited a potential association with (CRC) (P = 0.017; OD 0.44; CI 95% 0.22–0.86; P ≤ 0.001; OD 0.24; CI 95% 0.11–0.50). The study reveals that single nucleotide polymorphisms (SNPs) in microRNA have a notable and distinct correlation with the heightened susceptibility to colorectal cancer (CRC).","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593933","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}
Pub Date : 2024-04-03DOI: 10.1186/s43042-024-00511-8
Nur Ain Azman, Zefarina Zulkafli, Nur Salwani Bakar, Mat Ghani Siti Nor Assyuhada, Siti Nur Nabeela A’ifah Mohammad
Iron deficiency contributes for over half of all anaemia cases, especially among women and children. Iron deficiency anaemia remains a serious public health concern worldwide. The aim of this study is to determine the association between the single nucleotide polymorphism rs235756 in the bone morphogenetic protein 2 (BMP2) gene and iron deficiency status. 104 total anaemic samples were selected from Hospital Universiti Sains Malaysia. ARMS-PCR was performed to genotype the rs235756 SNP in the 104 samples. The genotype distribution of BMP2 rs235756 showed that AG genotypes had the highest frequency 51(86.4%) followed by GG 6(10.2%) and AA 2(3.4%) in IDA group, whereas AG 42(93.3%), AA 2(4.4%) and GG 1(2.2%) were found in the other anaemia group. The minor allele frequency in BMP 2 rs235756 from this study (0.514) was not similar to the East Asian (EAS) population (0.135); however, the allelic frequency showed significant association between these two. The mean of total iron binding capacity level differed significantly between homozygous-dominant AA and AG + GG genotypes (P < 0.05) but no significant difference for the mean of haematological parameter, ferritin and serum iron. In future clinical settings, this finding can potentially be as a guide in the early prediction for IDA patients through the genetic testing.
在所有贫血症病例中，缺铁症占一半以上，尤其是在妇女和儿童中。缺铁性贫血仍是全球严重的公共卫生问题。本研究旨在确定骨形态发生蛋白 2（BMP2）基因中的单核苷酸多态性 rs235756 与缺铁状况之间的关联。研究人员从马来西亚理科大学医院选取了104个贫血样本。对 104 个样本中的 rs235756 SNP 进行了 ARMS-PCR 基因分型。BMP2 rs235756的基因型分布显示，在IDA组中，AG基因型的频率最高，为51（86.4%），其次是GG 6（10.2%）和AA 2（3.4%）；而在其他贫血组中，AG 42（93.3%）、AA 2（4.4%）和GG 1（2.2%）。本研究中 BMP 2 rs235756 的小等位基因频率（0.514）与东亚（EAS）人群（0.135）并不相似，但二者的等位基因频率有显著关联。同卵显性 AA 基因型和 AG + GG 基因型的总铁结合能力平均值有显著差异（P < 0.05），但血液学参数、铁蛋白和血清铁的平均值无显著差异。在未来的临床环境中，这一发现有可能成为通过基因检测早期预测 IDA 患者的指南。
{"title":"Association of single nucleotide polymorphism at BMP2 gene with iron deficiency status among anaemic patients in Hospital Universiti Sains Malaysia","authors":"Nur Ain Azman, Zefarina Zulkafli, Nur Salwani Bakar, Mat Ghani Siti Nor Assyuhada, Siti Nur Nabeela A’ifah Mohammad","doi":"10.1186/s43042-024-00511-8","DOIUrl":"https://doi.org/10.1186/s43042-024-00511-8","url":null,"abstract":"Iron deficiency contributes for over half of all anaemia cases, especially among women and children. Iron deficiency anaemia remains a serious public health concern worldwide. The aim of this study is to determine the association between the single nucleotide polymorphism rs235756 in the bone morphogenetic protein 2 (BMP2) gene and iron deficiency status. 104 total anaemic samples were selected from Hospital Universiti Sains Malaysia. ARMS-PCR was performed to genotype the rs235756 SNP in the 104 samples. The genotype distribution of BMP2 rs235756 showed that AG genotypes had the highest frequency 51(86.4%) followed by GG 6(10.2%) and AA 2(3.4%) in IDA group, whereas AG 42(93.3%), AA 2(4.4%) and GG 1(2.2%) were found in the other anaemia group. The minor allele frequency in BMP 2 rs235756 from this study (0.514) was not similar to the East Asian (EAS) population (0.135); however, the allelic frequency showed significant association between these two. The mean of total iron binding capacity level differed significantly between homozygous-dominant AA and AG + GG genotypes (P < 0.05) but no significant difference for the mean of haematological parameter, ferritin and serum iron. In future clinical settings, this finding can potentially be as a guide in the early prediction for IDA patients through the genetic testing.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593941","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}
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