Pub Date : 2024-08-30DOI: 10.1186/s43042-024-00571-w
Basma A. Ibrahim, Eman S. Nagdy, Essam Nour Eldin, Alaa M. I. Khalil, Ahmed K. El-Taher
Breast cancer (BC) is the most prevalent cancer and the leading cause of cancer-related deaths in women globally. Cysteine protease cathepsin-B has been implicated in various human malignancies and is involved in malignancy progression and metastasis. This study aimed to evaluate the circulating levels of cathepsin-B, interleukin-6 (IL-6), and CA15-3, a cancer antigen, as biomarkers for tumors in women with both localized and metastatic BC. The study employed a case-control design, enrolling 108 participants categorized into three groups: healthy individuals, those with localized BC, and those with metastatic BC. The relative mRNA expression of cathepsin-B in blood samples was assessed using qRT-PCR. Additionally, serum levels of IL-6 and CA15-3 were quantified using ELISA. The relative mRNA expression of cathepsin-B, IL-6 levels, and CA15-3 levels were significantly higher in metastatic BC cases than in localized BC cases and the control group (p-value < 0.001). A statistically significant positive correlation was also found between cathepsin-B and both IL-6 and CA15-3 (r = 0.905, r = 0.667, and p < 0.001), respectively. The findings indicate a strong correlation between the interaction of the proteolytic enzyme cathepsin-B and IL-6 with the unfavorable prognosis of BC. This relationship may serve as a potential indicator and a promising target for therapy in BC treatment.
{"title":"Assessment of interleukin-6 and cathepsin-B gene expression in breast cancer women","authors":"Basma A. Ibrahim, Eman S. Nagdy, Essam Nour Eldin, Alaa M. I. Khalil, Ahmed K. El-Taher","doi":"10.1186/s43042-024-00571-w","DOIUrl":"https://doi.org/10.1186/s43042-024-00571-w","url":null,"abstract":"Breast cancer (BC) is the most prevalent cancer and the leading cause of cancer-related deaths in women globally. Cysteine protease cathepsin-B has been implicated in various human malignancies and is involved in malignancy progression and metastasis. This study aimed to evaluate the circulating levels of cathepsin-B, interleukin-6 (IL-6), and CA15-3, a cancer antigen, as biomarkers for tumors in women with both localized and metastatic BC. The study employed a case-control design, enrolling 108 participants categorized into three groups: healthy individuals, those with localized BC, and those with metastatic BC. The relative mRNA expression of cathepsin-B in blood samples was assessed using qRT-PCR. Additionally, serum levels of IL-6 and CA15-3 were quantified using ELISA. The relative mRNA expression of cathepsin-B, IL-6 levels, and CA15-3 levels were significantly higher in metastatic BC cases than in localized BC cases and the control group (p-value < 0.001). A statistically significant positive correlation was also found between cathepsin-B and both IL-6 and CA15-3 (r = 0.905, r = 0.667, and p < 0.001), respectively. The findings indicate a strong correlation between the interaction of the proteolytic enzyme cathepsin-B and IL-6 with the unfavorable prognosis of BC. This relationship may serve as a potential indicator and a promising target for therapy in BC treatment.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"37 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177519","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 : 2024-08-20DOI: 10.1186/s43042-024-00565-8
Kaniha Sivakumar, Usha Subbiah
Lipocalin-2 (LCN2), a neutrophil gelatinase-associated protein, plays an important role in iron homeostasis, infection, and inflammation. Polymorphism in the LCN2 gene is linked to various diseases such as cardiovascular disease, renal damage, and colorectal and pancreatic cancer. Identifying deleterious functional non-synonymous SNPs in the LCN2 gene is crucial in understanding how these genetic variations affect its structure and function. Several in silico tools such as SIFT, Polyphen-2, PROVEAN, PREDICT SNP, MAPP, and SNAP2 followed by I-MUTANT 2.0, MUpro, ConSurf, and NetsurfP-2.0, secondary structure of the protein by SOPMA and PSIPRED, while its interaction with other genes and proteins was analyzed using GeneMANIA and STRING, respectively, and AlphaFold for protein's 3D structure prediction. The study identified 6 potentially harmful nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) and their structure and function were analyzed using prediction tools. I-MUTANT 2.0 predicted an increase in stability with the nsSNPs rs139418967, while the other shows decrease in protein stability with the 6 nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) which was validated using MUpro. ConSurf identified the 6 high-risk nsSNPs to be in the conserved regions of the protein. The result showed that rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, and rs368926734 were found to be highly conserved and the variant amino acids. According to NetsurfP-2.0 server, the result showed that rs11556770 (Q39H), rs139418967 (L6P), rs368926734 (Y135H) were predicted to be exposed and rs142623708 (M71I), rs200107414 (Y52C), rs368926734 (Y135) were buried. The PSIPRED server analysis indicated that the predominant secondary structure was a strand, with lesser occurrences of coil and helix. Overall, the study identified detrimental nsSNPs of LCN2 using computational analysis which could be used for large population-based investigations and diagnosis.
{"title":"Computational analysis of non-synonymous SNPs in the human LCN2 gene","authors":"Kaniha Sivakumar, Usha Subbiah","doi":"10.1186/s43042-024-00565-8","DOIUrl":"https://doi.org/10.1186/s43042-024-00565-8","url":null,"abstract":"Lipocalin-2 (LCN2), a neutrophil gelatinase-associated protein, plays an important role in iron homeostasis, infection, and inflammation. Polymorphism in the LCN2 gene is linked to various diseases such as cardiovascular disease, renal damage, and colorectal and pancreatic cancer. Identifying deleterious functional non-synonymous SNPs in the LCN2 gene is crucial in understanding how these genetic variations affect its structure and function. Several in silico tools such as SIFT, Polyphen-2, PROVEAN, PREDICT SNP, MAPP, and SNAP2 followed by I-MUTANT 2.0, MUpro, ConSurf, and NetsurfP-2.0, secondary structure of the protein by SOPMA and PSIPRED, while its interaction with other genes and proteins was analyzed using GeneMANIA and STRING, respectively, and AlphaFold for protein's 3D structure prediction. The study identified 6 potentially harmful nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) and their structure and function were analyzed using prediction tools. I-MUTANT 2.0 predicted an increase in stability with the nsSNPs rs139418967, while the other shows decrease in protein stability with the 6 nsSNPs (rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, rs368926734) which was validated using MUpro. ConSurf identified the 6 high-risk nsSNPs to be in the conserved regions of the protein. The result showed that rs11556770, rs139418967, rs142623708, rs200107414, rs201365744, and rs368926734 were found to be highly conserved and the variant amino acids. According to NetsurfP-2.0 server, the result showed that rs11556770 (Q39H), rs139418967 (L6P), rs368926734 (Y135H) were predicted to be exposed and rs142623708 (M71I), rs200107414 (Y52C), rs368926734 (Y135) were buried. The PSIPRED server analysis indicated that the predominant secondary structure was a strand, with lesser occurrences of coil and helix. Overall, the study identified detrimental nsSNPs of LCN2 using computational analysis which could be used for large population-based investigations and diagnosis.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"9 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177520","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 : 2024-08-07DOI: 10.1186/s43042-024-00561-y
Si Chen, Xiaoli Zeng, Xu Ma, Haixia Luan, Rui Nie, Yan Wang, Hua Liao, Lili Pan, Hui Yuan
Recent studies have indicated a potential association between giant cell arteritis (GCA) and diabetes mellitus, encompassing both type 1 diabetes (T1D) and type 2 diabetes (T2D). However, the exact nature of this relationship requires further investigation to be fully elucidated. Genetic links between T1D/T2D and GCA were explored using data from genome-wide association studies available to the public, focusing on populations of European ancestry. We applied a bidirectional mendelian randomization (MR) approach to assess the potential association between these diseases. Confirmatory analyses, including additional datasets and a comprehensive meta-analysis, were utilized. The inverse-variance-weighted (IVW) method was applied to pinpoint heterogeneity and pleiotropy, while subsequent sensitivity analyses aimed to trace the origins of any heterogeneity. Initial analysis demonstrated a correlation between T1D and an elevated likelihood of developing GCA (IVW odds ratio = 1.33, with a 95% confidence interval of 1.22–1.46, and a P-value of 9.42E−10). The causal association was verified through four validation datasets and meta-analysis (all P-value < 0.001). However, the reverse MR analysis was unable to detect any genetic basis for the increased risk of T1D due to GCA. Furthermore, we could not establish any causal links between T2D and GCA. T1D patients may have a higher risk of developing GCA, whereas an inverse causal relationship was not evident. Furthermore, no causal relationship was detected between T2D and GCA. These insights shed light on the possible pathological mechanisms underlying GCA and may influence the future clinical handling of both T1D and GCA.
{"title":"Association between diabetes mellitus and giant cell arteritis: a bidirectional 2-sample mendelian randomization study","authors":"Si Chen, Xiaoli Zeng, Xu Ma, Haixia Luan, Rui Nie, Yan Wang, Hua Liao, Lili Pan, Hui Yuan","doi":"10.1186/s43042-024-00561-y","DOIUrl":"https://doi.org/10.1186/s43042-024-00561-y","url":null,"abstract":"Recent studies have indicated a potential association between giant cell arteritis (GCA) and diabetes mellitus, encompassing both type 1 diabetes (T1D) and type 2 diabetes (T2D). However, the exact nature of this relationship requires further investigation to be fully elucidated. Genetic links between T1D/T2D and GCA were explored using data from genome-wide association studies available to the public, focusing on populations of European ancestry. We applied a bidirectional mendelian randomization (MR) approach to assess the potential association between these diseases. Confirmatory analyses, including additional datasets and a comprehensive meta-analysis, were utilized. The inverse-variance-weighted (IVW) method was applied to pinpoint heterogeneity and pleiotropy, while subsequent sensitivity analyses aimed to trace the origins of any heterogeneity. Initial analysis demonstrated a correlation between T1D and an elevated likelihood of developing GCA (IVW odds ratio = 1.33, with a 95% confidence interval of 1.22–1.46, and a P-value of 9.42E−10). The causal association was verified through four validation datasets and meta-analysis (all P-value < 0.001). However, the reverse MR analysis was unable to detect any genetic basis for the increased risk of T1D due to GCA. Furthermore, we could not establish any causal links between T2D and GCA. T1D patients may have a higher risk of developing GCA, whereas an inverse causal relationship was not evident. Furthermore, no causal relationship was detected between T2D and GCA. These insights shed light on the possible pathological mechanisms underlying GCA and may influence the future clinical handling of both T1D and GCA.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"22 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141937882","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 : 2024-08-06DOI: 10.1186/s43042-024-00563-w
Ankita Debnath, Sukanta Nath
Acute myeloid leukemia (AML) is a heterogeneous disorder that is characterized by clonal expansion of immature "blast cells" in the bone marrow and peripheral circulation, resulting in bone marrow failure and inefficient erythropoiesis. The identification of numerous recurrent genetic mutations such as NPM1, CEBPA, and FLT3-ITD has stratified AML into favorable, intermediate, and adverse-risk groups, respectively, along with a cytogenetic profile that carries a considerably different prognosis among these groups. For post-induction treatment, cytogenetics and genetic mutation testing continue to be vital prognostic tools. Despite advancements, including an increased understanding of biology and new drug targets, the cornerstone of treatment still consists of a combination of cytarabine- and anthracycline-based regimens. The majority of patients eventually relapse and die of the disease, especially the elderly population. This review describes the prognosis of different molecular markers and the major recent advancements in the treatment of AML.
{"title":"Prognosis and treatment in acute myeloid leukemia: a comprehensive review","authors":"Ankita Debnath, Sukanta Nath","doi":"10.1186/s43042-024-00563-w","DOIUrl":"https://doi.org/10.1186/s43042-024-00563-w","url":null,"abstract":"Acute myeloid leukemia (AML) is a heterogeneous disorder that is characterized by clonal expansion of immature \"blast cells\" in the bone marrow and peripheral circulation, resulting in bone marrow failure and inefficient erythropoiesis. The identification of numerous recurrent genetic mutations such as NPM1, CEBPA, and FLT3-ITD has stratified AML into favorable, intermediate, and adverse-risk groups, respectively, along with a cytogenetic profile that carries a considerably different prognosis among these groups. For post-induction treatment, cytogenetics and genetic mutation testing continue to be vital prognostic tools. Despite advancements, including an increased understanding of biology and new drug targets, the cornerstone of treatment still consists of a combination of cytarabine- and anthracycline-based regimens. The majority of patients eventually relapse and die of the disease, especially the elderly population. This review describes the prognosis of different molecular markers and the major recent advancements in the treatment of AML.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"22 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141937950","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}
Hepatocellular carcinoma (HCC) constitutes an important contributor to fatalities. Coronavirus disease 2019 (COVID-19) frequently presents with complications such as respiratory distress, systemic inflammatory responses, and damage to various organs. Several studies have investigated the relationship between COVID-19 and mortality in patients with liver cancer, but there are few research on the relationship between them. This study is to explore the correlation between the two diseases and drugs treating them. The Gene Expression Omnibus (GEO) database provides gene datasets of COVID-19 patients and HCC patients. Through differential gene analysis and weighted gene co-expression network analysis, we determined 223 genes represented in HCC and COVID-19. We then used functional annotation, protein–protein interaction network construction, predictive model development and verification, prognostic value analysis, and miRNA–gene network construction. Besides, we created a drug–hub–gene network by predicting possible medications that interact with hub genes using the Drug–Gene Interaction Database (DGIdb). Ultimately, we applied immunohistochemistry to ascertain the hub genes expression. This study revealed that eight core genes (RRM2, TPX2, DTL, CDT1, TYMS, CDCA5, CDC25C, and HJURP) co-existed in both HCC and COVID-19 and were differentially expressed in both HCC and normal tissues.CDC25C, RRM2, CDCA5, and HJURP had diagnostic value (AUC > 0.8) and prognostic value (adjusted P-value < 0.05). Genome enrichment analysis indicated that eight genes may function in liver cancer through engagement in the cell cycle, DNA replication, etc. In liver cancer samples, these genes were significantly and adversely associated with plasma cells while RRM2 was positively associated with neutrophil and NK cell activation and with dendritic cell resting. Using the miRNAnet database and DGIdb, 9 transcription factors, 7 miRNAs, and 51 drugs or molecular compounds were predicted to interact with the hub genes. Finally, RRM2 expression showed significant variation in clinical specimens, and analysis of the association of RRM2 with immunomodulators indicated that RRM2 was closely connected to MICB and CD276. Our study revealed several metabolic genes related to HCC and COVID-19. Moreover, potential drugs related to central genes were predicted. These findings may provide new ideas for treating COVID-19 and HCC.
{"title":"Exploring potential therapeutic strategy for hepatocellular carcinoma and COVID-19 using bioinformatics analysis","authors":"Jiayan Tang, Zaiyong Yang, Huotang Qin, Yu Huang, Minqing Li, Qing Deng, Ling Li, Xiaolong Li","doi":"10.1186/s43042-024-00560-z","DOIUrl":"https://doi.org/10.1186/s43042-024-00560-z","url":null,"abstract":"Hepatocellular carcinoma (HCC) constitutes an important contributor to fatalities. Coronavirus disease 2019 (COVID-19) frequently presents with complications such as respiratory distress, systemic inflammatory responses, and damage to various organs. Several studies have investigated the relationship between COVID-19 and mortality in patients with liver cancer, but there are few research on the relationship between them. This study is to explore the correlation between the two diseases and drugs treating them. The Gene Expression Omnibus (GEO) database provides gene datasets of COVID-19 patients and HCC patients. Through differential gene analysis and weighted gene co-expression network analysis, we determined 223 genes represented in HCC and COVID-19. We then used functional annotation, protein–protein interaction network construction, predictive model development and verification, prognostic value analysis, and miRNA–gene network construction. Besides, we created a drug–hub–gene network by predicting possible medications that interact with hub genes using the Drug–Gene Interaction Database (DGIdb). Ultimately, we applied immunohistochemistry to ascertain the hub genes expression. This study revealed that eight core genes (RRM2, TPX2, DTL, CDT1, TYMS, CDCA5, CDC25C, and HJURP) co-existed in both HCC and COVID-19 and were differentially expressed in both HCC and normal tissues.CDC25C, RRM2, CDCA5, and HJURP had diagnostic value (AUC > 0.8) and prognostic value (adjusted P-value < 0.05). Genome enrichment analysis indicated that eight genes may function in liver cancer through engagement in the cell cycle, DNA replication, etc. In liver cancer samples, these genes were significantly and adversely associated with plasma cells while RRM2 was positively associated with neutrophil and NK cell activation and with dendritic cell resting. Using the miRNAnet database and DGIdb, 9 transcription factors, 7 miRNAs, and 51 drugs or molecular compounds were predicted to interact with the hub genes. Finally, RRM2 expression showed significant variation in clinical specimens, and analysis of the association of RRM2 with immunomodulators indicated that RRM2 was closely connected to MICB and CD276. Our study revealed several metabolic genes related to HCC and COVID-19. Moreover, potential drugs related to central genes were predicted. These findings may provide new ideas for treating COVID-19 and HCC.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"154 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141937885","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 : 2024-08-04DOI: 10.1186/s43042-024-00562-x
Xin Zhao, Pan Wu, Zhi Yang, Rong-Rong Miao
Methotrexate is a widely used drug in clinical practice for the treatment of collagen vascular diseases and malignant tumors. It has good anti-inflammatory and anti-proliferative effects, but the cytotoxicity of methotrexate can cause various adverse reactions in patients. Studies have shown that the sensitivity and tolerance of different individuals to methotrexate is different. There are many reasons for this difference. Among them, genetic polymorphism is one of the main factors that cause individual differences. This article provides an overview of the genetic polymorphisms of key proteins involved in methotrexate metabolism and transport, such as MTHFR, FPGS, γ-GGH, ABC transporter, OATPs, SLC, TS and DHFR, are related to their efficacy and adverse reactions. The aim is to clarify the impact of genetic polymorphisms on the efficacy and adverse effects of methotrexate at the pharmacogenomic level, in order to provide a basis for the clinical application of methotrexate.
{"title":"Relationship between the efficacy and adverse effects of methotrexate and gene polymorphism","authors":"Xin Zhao, Pan Wu, Zhi Yang, Rong-Rong Miao","doi":"10.1186/s43042-024-00562-x","DOIUrl":"https://doi.org/10.1186/s43042-024-00562-x","url":null,"abstract":"Methotrexate is a widely used drug in clinical practice for the treatment of collagen vascular diseases and malignant tumors. It has good anti-inflammatory and anti-proliferative effects, but the cytotoxicity of methotrexate can cause various adverse reactions in patients. Studies have shown that the sensitivity and tolerance of different individuals to methotrexate is different. There are many reasons for this difference. Among them, genetic polymorphism is one of the main factors that cause individual differences. This article provides an overview of the genetic polymorphisms of key proteins involved in methotrexate metabolism and transport, such as MTHFR, FPGS, γ-GGH, ABC transporter, OATPs, SLC, TS and DHFR, are related to their efficacy and adverse reactions. The aim is to clarify the impact of genetic polymorphisms on the efficacy and adverse effects of methotrexate at the pharmacogenomic level, in order to provide a basis for the clinical application of methotrexate.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"6 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141937886","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 : 2024-07-31DOI: 10.1186/s43042-024-00552-z
Amal El-Beshlawy, Azza A. G. Tantawy, Rabah M. Shawky, Solaf M. Elsayed, Iman M. Marzouk, S. Elgawhary, Hadeer Abdelghaffar, Usama El Safy, Khaled Eid, Khalid I. EISayh, Ahmed Megahed, Amira Adly, Eman M. Sherif, Mervat A. M. Youssef, Manar Mohamed Fathy, Nouran Yousef Salah, Sherine M. Elzeiny, Eslam Rabie Abdel Aziz EI Bakky, Ekram Fateen
Gaucher disease (GD), an autosomal recessive, lysosomal storage disorder, is caused due to mutations in the glucocerebrosidase (GBA) gene. GD can occur at any age and is classified as type 1 (non-neurologic), type 2 (infantile form, with acute early neurologic manifestation), and type 3 (subacute/chronic neuropathic form). The rarity of the disease and its overlapping symptoms with other diseases increase the delay in diagnosis. The Egyptian cohort of patients with GD is specifically different regarding the prevalence of type 3 as well as the severity and progression of the disease. The unavailability of precise diagnostic tests and lack of awareness among clinicians are the current challenges associated with diagnosing and managing GD in Egypt. An expert panel meeting was convened with 19 experts from Egypt to address the current unmet challenges in the diagnosis and management of GD from the region and to develop country-specific diagnostic algorithms based on the existing literature for pediatric and adult groups. In addition, management strategies and preventive measures were also discussed. The algorithms presented in this review can be implemented in clinical practice for the timely diagnosis of patients with GD in Egypt. Early diagnosis is crucial in selecting the best treatment for patients with GD, and evidence suggests that early initiation of therapy can result in better outcomes. The evidence-based expert opinion presented in this review will help clinicians in the early initial diagnosis of GD in Egypt, leading to appropriate management of the disease.
{"title":"Diagnosis and management of patients with Gaucher disease: an Egyptian expert opinion","authors":"Amal El-Beshlawy, Azza A. G. Tantawy, Rabah M. Shawky, Solaf M. Elsayed, Iman M. Marzouk, S. Elgawhary, Hadeer Abdelghaffar, Usama El Safy, Khaled Eid, Khalid I. EISayh, Ahmed Megahed, Amira Adly, Eman M. Sherif, Mervat A. M. Youssef, Manar Mohamed Fathy, Nouran Yousef Salah, Sherine M. Elzeiny, Eslam Rabie Abdel Aziz EI Bakky, Ekram Fateen","doi":"10.1186/s43042-024-00552-z","DOIUrl":"https://doi.org/10.1186/s43042-024-00552-z","url":null,"abstract":"Gaucher disease (GD), an autosomal recessive, lysosomal storage disorder, is caused due to mutations in the glucocerebrosidase (GBA) gene. GD can occur at any age and is classified as type 1 (non-neurologic), type 2 (infantile form, with acute early neurologic manifestation), and type 3 (subacute/chronic neuropathic form). The rarity of the disease and its overlapping symptoms with other diseases increase the delay in diagnosis. The Egyptian cohort of patients with GD is specifically different regarding the prevalence of type 3 as well as the severity and progression of the disease. The unavailability of precise diagnostic tests and lack of awareness among clinicians are the current challenges associated with diagnosing and managing GD in Egypt. An expert panel meeting was convened with 19 experts from Egypt to address the current unmet challenges in the diagnosis and management of GD from the region and to develop country-specific diagnostic algorithms based on the existing literature for pediatric and adult groups. In addition, management strategies and preventive measures were also discussed. The algorithms presented in this review can be implemented in clinical practice for the timely diagnosis of patients with GD in Egypt. Early diagnosis is crucial in selecting the best treatment for patients with GD, and evidence suggests that early initiation of therapy can result in better outcomes. The evidence-based expert opinion presented in this review will help clinicians in the early initial diagnosis of GD in Egypt, leading to appropriate management of the disease.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"4 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866643","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 : 2024-07-31DOI: 10.1186/s43042-024-00557-8
Emmanuel Suluba, James Masaganya, Erasto Mbugi, Mwinyi Masala, Jackline Mathew, Henry Mruma, Liu Shuwei
The evolutionally conserved homeobox transcription factor NKX2-5 has been at the forefront in the field of cardiac biology, providing molecular insights into the mechanisms of cardiac development and disease. This homodomain transcription factor is a central regulator of cardiac development and is expressed in both the first and second heart fields (FHF and SHF). Mutations in the NKX2-5 gene have been linked to sporadic cases of congenital heart disease (CHD), making it a significant target for research and study. While several studies have been conducted on Caucasian populations, there is a dearth of knowledge on the effects of NKX2-5 gene mutations in other settings, underscoring the need for further investigation. Due to differences in geographical and ancestral origin, we hypothesize that mutations may vary across different populations. Understanding the genetic factors that cause CHD is essential for providing effective genetic counseling and developing strategies for risk reduction. Additionally, identification of NKX2-5 mutations in individuals with CHDs is crucial because patients with CHDs are at a higher risk of progressive conduction disease and sudden cardiac death, and genetic information is taken into consideration while making decisions regarding pacemakers and implantable cardiac defibrillators. To determine the risk of congenital heart disease among infants, we conducted a study where we sequenced the exon 1 and exon 2 of NKX 2.5 in patients with sporadic CHDs, with the aim of identifying mutations in the NKX2.5 gene. In this study, a novel frame-shift disease-causing mutation was discovered in patients with atrial-ventricular septal defect. The mutation, identified as c95_95 del A; cDNA.369–369 delA; g 369–369 delA, resulted in the substitution of phenylalanine to leucine (F295L), which in turn caused a truncated NKX2.5 protein. In addition, a non-synonymous mutation, g 316C > T; cDNA 316C > T leucine to arginine (L37R) substitution, was found in a patient with the tetralogy of Fallot, affecting protein function. Furthermore, a novel non-synonymous mutation identified as g 2295–2298; cDNA 755–758 delins AGGG, was predicted by mutation taster to be disease-causing in a ventricular septal defect. It is worth noting that none of these mutations were found among the control subjects, highlighting their potential significance in the pathogenesis of these cardiac defects. Mutations in the NKX2.5 gene are associated with congenital heart diseases and provide molecular insight into the pathogenesis of congenital heart diseases. We recommend that patients with NKX2.5 mutations have periodic screening for cardiac conduction abnormalities and be evaluated for potential implanted cardiac defibrillators and pacemakers.
{"title":"NKX2.5 coding exons sequencing reveals novel non-synonymous mutations in patients with sporadic congenital heart diseases among the Tanzanian population","authors":"Emmanuel Suluba, James Masaganya, Erasto Mbugi, Mwinyi Masala, Jackline Mathew, Henry Mruma, Liu Shuwei","doi":"10.1186/s43042-024-00557-8","DOIUrl":"https://doi.org/10.1186/s43042-024-00557-8","url":null,"abstract":"The evolutionally conserved homeobox transcription factor NKX2-5 has been at the forefront in the field of cardiac biology, providing molecular insights into the mechanisms of cardiac development and disease. This homodomain transcription factor is a central regulator of cardiac development and is expressed in both the first and second heart fields (FHF and SHF). Mutations in the NKX2-5 gene have been linked to sporadic cases of congenital heart disease (CHD), making it a significant target for research and study. While several studies have been conducted on Caucasian populations, there is a dearth of knowledge on the effects of NKX2-5 gene mutations in other settings, underscoring the need for further investigation. Due to differences in geographical and ancestral origin, we hypothesize that mutations may vary across different populations. Understanding the genetic factors that cause CHD is essential for providing effective genetic counseling and developing strategies for risk reduction. Additionally, identification of NKX2-5 mutations in individuals with CHDs is crucial because patients with CHDs are at a higher risk of progressive conduction disease and sudden cardiac death, and genetic information is taken into consideration while making decisions regarding pacemakers and implantable cardiac defibrillators. To determine the risk of congenital heart disease among infants, we conducted a study where we sequenced the exon 1 and exon 2 of NKX 2.5 in patients with sporadic CHDs, with the aim of identifying mutations in the NKX2.5 gene. In this study, a novel frame-shift disease-causing mutation was discovered in patients with atrial-ventricular septal defect. The mutation, identified as c95_95 del A; cDNA.369–369 delA; g 369–369 delA, resulted in the substitution of phenylalanine to leucine (F295L), which in turn caused a truncated NKX2.5 protein. In addition, a non-synonymous mutation, g 316C > T; cDNA 316C > T leucine to arginine (L37R) substitution, was found in a patient with the tetralogy of Fallot, affecting protein function. Furthermore, a novel non-synonymous mutation identified as g 2295–2298; cDNA 755–758 delins AGGG, was predicted by mutation taster to be disease-causing in a ventricular septal defect. It is worth noting that none of these mutations were found among the control subjects, highlighting their potential significance in the pathogenesis of these cardiac defects. Mutations in the NKX2.5 gene are associated with congenital heart diseases and provide molecular insight into the pathogenesis of congenital heart diseases. We recommend that patients with NKX2.5 mutations have periodic screening for cardiac conduction abnormalities and be evaluated for potential implanted cardiac defibrillators and pacemakers.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"49 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866646","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}
Spinal muscular atrophy (SMA) is a group of motor neuron diseases. In 95% of SMA patients, the telomeric copy of the SMN gene (SMN1) is homozygously deleted. Due to the autosomal recessive pattern of SMA inheritance, individuals with a family history of SMA are at risk of being carriers. A total of 622 individuals from SMA families, including parents, siblings, and first, second, and third-degree relatives, were recruited to the neuro-genetic clinic of Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. SMA cases and suspected carriers were referred to the genetic laboratory. Pregnant women underwent amniocentesis and chorionic villi sampling at 12–14 gestational weeks. RFLP-PCR and real-time PCR were performed for symptomatic and asymptomatic individuals (possible carriers), respectively. RFLP and real-time PCR were performed for amniotic fluid and chorionic villi samples. The study enrolled 622 subjects from SMA-affected families, including 159 fetuses and 463 non-fetuses. Two samples were missing. A total of 268 individuals (43.2%) were healthy (wild type), 187 individuals (30.1%) were heterozygous for exon deletion of SMN1, and 143 individuals (23%) were homozygous for exon deletion of SMN1. Four individuals (0.6%) showed three copies of the SMN1 gene. The frequency of carriers with two SMN1 copies on a single chromosome (cis) was estimated at 2.9% (18/622), and the total rate of carriers was approximately 21.8%. Considering the high rate of SMA carriers in this study, genetic counseling and definitive prenatal diagnosis are of utmost importance for reducing the psychosocial burden of the SMA disease among Iranian families.
脊髓性肌萎缩症（SMA）是一组运动神经元疾病。在 95% 的 SMA 患者中，SMN 基因（SMN1）的端粒拷贝被同源染色体删除。由于 SMA 的遗传方式为常染色体隐性遗传，有 SMA 家族史的人有可能成为携带者。伊朗马什哈德市马什哈德医科大学盖姆医院神经遗传诊所共招募了 622 名 SMA 家族成员，包括父母、兄弟姐妹、一级、二级和三级亲属。SMA 病例和疑似携带者被转介到基因实验室。孕妇在妊娠 12-14 周时接受羊膜腔穿刺术和绒毛取样。分别对有症状和无症状者（可能的携带者）进行了 RFLP-PCR 和实时 PCR 检测。对羊水和绒毛样本进行了 RFLP 和实时 PCR 检测。该研究共纳入了 622 名来自 SMA 受影响家庭的受试者，其中包括 159 名胎儿和 463 名非胎儿。有两个样本缺失。共有268人（43.2%）为健康（野生型），187人（30.1%）为SMN1外显子缺失杂合子，143人（23%）为SMN1外显子缺失同源杂合子。4人（0.6%）的SMN1基因有三个拷贝。单条染色体上有两个SMN1基因拷贝（顺式）的携带者频率估计为2.9%（18/622），携带者总比率约为21.8%。考虑到本研究中 SMA 携带者的比例较高，遗传咨询和明确的产前诊断对于减轻 SMA 疾病给伊朗家庭带来的社会心理负担至关重要。
{"title":"The prevalence of SMN gene deletion/duplication in spinal muscular atrophy families referred to neuro-genetic centers of Mashhad, Iran","authors":"Mohammad Shariati, Alireza Davoudi, Reza Boostani, Farah Ashrafzadeh, Mehran Beiraghi Toosi, Nafiseh Todarbary, Javad Akhondian, Narges Hashemi, Ariane Sadr-Nabavi","doi":"10.1186/s43042-024-00551-0","DOIUrl":"https://doi.org/10.1186/s43042-024-00551-0","url":null,"abstract":"Spinal muscular atrophy (SMA) is a group of motor neuron diseases. In 95% of SMA patients, the telomeric copy of the SMN gene (SMN1) is homozygously deleted. Due to the autosomal recessive pattern of SMA inheritance, individuals with a family history of SMA are at risk of being carriers. A total of 622 individuals from SMA families, including parents, siblings, and first, second, and third-degree relatives, were recruited to the neuro-genetic clinic of Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. SMA cases and suspected carriers were referred to the genetic laboratory. Pregnant women underwent amniocentesis and chorionic villi sampling at 12–14 gestational weeks. RFLP-PCR and real-time PCR were performed for symptomatic and asymptomatic individuals (possible carriers), respectively. RFLP and real-time PCR were performed for amniotic fluid and chorionic villi samples. The study enrolled 622 subjects from SMA-affected families, including 159 fetuses and 463 non-fetuses. Two samples were missing. A total of 268 individuals (43.2%) were healthy (wild type), 187 individuals (30.1%) were heterozygous for exon deletion of SMN1, and 143 individuals (23%) were homozygous for exon deletion of SMN1. Four individuals (0.6%) showed three copies of the SMN1 gene. The frequency of carriers with two SMN1 copies on a single chromosome (cis) was estimated at 2.9% (18/622), and the total rate of carriers was approximately 21.8%. Considering the high rate of SMA carriers in this study, genetic counseling and definitive prenatal diagnosis are of utmost importance for reducing the psychosocial burden of the SMA disease among Iranian families.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"50 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866645","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 : 2024-07-29DOI: 10.1186/s43042-024-00556-9
Chen Huang, Wenwen Zhang
We described a case of abdominal aortic aneurysm complicated by type B thoracic aortic dissection, in whom molecular analysis revealed a pathogenic TGFBR1 missense mutation. A 36-year-old woman was admitted to our hospital with sudden onset of back pain. Computed tomography angiogram demonstrated descending aortic dissection extending into the abdominal aorta aneurysm. Whole-exome sequencing and subsequent Sanger sequencing confirmed a pathogenic mutation in the TGFBRI gene (NM_004612.4: c.605C > T; p.Ala202Val). She refused to receive surgery and died one month later. To our knowledge, this is the first documented case of the TGFBR1 gene mutation who suffered from abdominal aortic aneurysm complicated by descending thoracic aortic dissection. Her rapid death underscores the importance of timely intervention in TGFBR1 mutation-positive patients.
{"title":"Abdominal aortic aneurysm complicated by descending thoracic aortic dissection in a patient with TGFBR1 mutation","authors":"Chen Huang, Wenwen Zhang","doi":"10.1186/s43042-024-00556-9","DOIUrl":"https://doi.org/10.1186/s43042-024-00556-9","url":null,"abstract":"We described a case of abdominal aortic aneurysm complicated by type B thoracic aortic dissection, in whom molecular analysis revealed a pathogenic TGFBR1 missense mutation. A 36-year-old woman was admitted to our hospital with sudden onset of back pain. Computed tomography angiogram demonstrated descending aortic dissection extending into the abdominal aorta aneurysm. Whole-exome sequencing and subsequent Sanger sequencing confirmed a pathogenic mutation in the TGFBRI gene (NM_004612.4: c.605C > T; p.Ala202Val). She refused to receive surgery and died one month later. To our knowledge, this is the first documented case of the TGFBR1 gene mutation who suffered from abdominal aortic aneurysm complicated by descending thoracic aortic dissection. Her rapid death underscores the importance of timely intervention in TGFBR1 mutation-positive patients.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"74 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866644","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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