Interleukins are potential therapeutic targets that can alter the prognosis and progression of inflammatory bowel disease (IBD). The roles of IL-6, IL-10, IL-17, and IL-23 have been extensively studied, setting the stage for the development of novel treatments for patients with IBD. Other cytokines have been less extensively studied. Members of the IL-20 family, mainly IL-19 and IL-24, are involved in the pathogenesis of IBD, but their exact role remains unclear. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of colonic Tregs in animal models of colitis and patients with IBD. IL-21 is involved in the Th1, Th2, and Th17 responses. Data support a promising future use of these interleukins as biomarkers of severe diseases and as potential therapeutic targets for novel monoclonal antibodies. This review aims to summarize the existing studies involving animal models of colitis and patients with IBD to clarify their role in the intestinal mucosa.
{"title":"The role of IL-19, IL-24, IL-21 and IL-33 in intestinal mucosa of inflammatory bowel disease: A narrative review","authors":"Alexandros Toskas , Stefanos Milias , Theodora Papamitsou , Soultana Meditskou , Nikolaos Kamperidis , Antonia Sioga","doi":"10.1016/j.ajg.2024.01.002","DOIUrl":"10.1016/j.ajg.2024.01.002","url":null,"abstract":"<div><div>Interleukins are potential therapeutic targets that can alter the prognosis and progression of inflammatory bowel disease (IBD). The roles of IL-6, IL-10, IL-17, and IL-23 have been extensively studied, setting the stage for the development of novel treatments for patients with IBD. Other cytokines have been less extensively studied. Members of the IL-20 family, mainly IL-19 and IL-24, are involved in the pathogenesis of IBD, but their exact role remains unclear. Similarly, IL-33, a newly identified cytokine, has been shown to control the Th1 effector response and the action of colonic Tregs in animal models of colitis and patients with IBD. IL-21 is involved in the Th1, Th2, and Th17 responses. Data support a promising future use of these interleukins as biomarkers of severe diseases and as potential therapeutic targets for novel monoclonal antibodies. This review aims to summarize the existing studies involving animal models of colitis and patients with IBD to clarify their role in the intestinal mucosa.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 9-17"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ajg.2025.01.002
Abdelmounem Eltayeib Abdo , Elmuhtady Said
Access to advanced medical procedures, such as gastrointestinal (GI) endoscopy, is critical for effective healthcare. In Sub-Saharan Africa, including Sudan, GI endoscopy services remain limited, posing significant barriers to early diagnosis and treatment of GI diseases. Expanding GI endoscopy services in Sudan and other regions of Sub-Saharan Africa is crucial to improve early detection, reduce mortality, and increase the cost-effectiveness of healthcare delivery.
This letter reviews the current state of GI endoscopy in Sudan, highlights the importance of enhancing this service, and proposes how the British Society of Gastroenterology (BSG) could assist in improving accessibility and quality.
{"title":"Advancing gastrointestinal endoscopy in Sub-Saharan Africa: Leveraging Sudan’s example and the potential role of the British Society of Gastroenterology (BSG)","authors":"Abdelmounem Eltayeib Abdo , Elmuhtady Said","doi":"10.1016/j.ajg.2025.01.002","DOIUrl":"10.1016/j.ajg.2025.01.002","url":null,"abstract":"<div><div>Access to advanced medical procedures, such as gastrointestinal (GI) endoscopy, is critical for effective healthcare. In Sub-Saharan Africa, including Sudan, GI endoscopy services remain limited, posing significant barriers to early diagnosis and treatment of GI diseases. Expanding GI endoscopy services in Sudan and other regions of Sub-Saharan Africa is crucial to improve early detection, reduce mortality, and increase the cost-effectiveness of healthcare delivery.</div><div>This letter reviews the current state of GI endoscopy in Sudan, highlights the importance of enhancing this service, and proposes how the British Society of Gastroenterology (BSG) could assist in improving accessibility and quality.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 139-140"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Personalized medicine is an emerging field that provides novel approaches to disease’s early diagnosis, prevention, treatment, and prognosis based on the patient’s criteria in gene expression, environmental factors, lifestyle, and diet. To date, hepatocellular carcinoma (HCC) is a significant global health burden, with an increasing incidence and significant death rates, despite advancements in surveillance, diagnosis, and therapeutic approaches. The majority of HCC lesions develop in patients with liver cirrhosis, carrying the risks of mortality associated with both the tumor burden and the cirrhosis.
New therapeutic agents involving immune checkpoint inhibitors and targeted agents have been developed for sequential or concomitant application for advanced HCC but only a tiny percentage of patients benefit from each approach. Moreover, clinicians encounter difficulties determining the most appropriate regimen for each patient. This emphasizes the need for a personalized treatment approach. In other words, patients should no longer undergo treatment based on their tumor’s histology but depending on the distinct molecular targets specific to their tumor biology. However, the utilization of precision medicine in managing HCC is still challenging.
This review aims to discuss the role of personalized medicine in diagnosing, managing, and defining the prognosis of HCC. We also discuss the role of liquid biopsy and their clinical applications for immunotherapies in HCC. More clinical studies are still necessary to improve the precision of biomarkers used in the treatment decision for patients with HCC.
{"title":"Personalized treatment approaches in hepatocellular carcinoma","authors":"Ahmed Ramadan , Mona Kaddah , Hend Shousha , Mohamed El-Kassas","doi":"10.1016/j.ajg.2024.08.003","DOIUrl":"10.1016/j.ajg.2024.08.003","url":null,"abstract":"<div><div>Personalized medicine is an emerging field that provides novel approaches to disease’s early diagnosis, prevention, treatment, and prognosis based on the patient’s criteria in gene expression, environmental factors, lifestyle, and diet. To date, hepatocellular carcinoma (HCC) is a significant global health burden, with an increasing incidence and significant death rates, despite advancements in surveillance, diagnosis, and therapeutic approaches. The majority of HCC lesions develop in patients with liver cirrhosis, carrying the risks of mortality associated with both the tumor burden and the cirrhosis.</div><div>New therapeutic agents involving immune checkpoint inhibitors and targeted agents have been developed for sequential or concomitant application for advanced HCC but only a tiny percentage of patients benefit from each approach. Moreover, clinicians encounter difficulties determining the most appropriate regimen for each patient. This emphasizes the need for a personalized treatment approach. In other words, patients should no longer undergo treatment based on their tumor’s histology but depending on the distinct molecular targets specific to their tumor biology. However, the utilization of precision medicine in managing HCC is still challenging.</div><div>This review aims to discuss the role of personalized medicine in diagnosing, managing, and defining the prognosis of HCC. We also discuss the role of liquid biopsy and their clinical applications for immunotherapies in HCC. More clinical studies are still necessary to improve the precision of biomarkers used in the treatment decision for patients with HCC.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 122-128"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ajg.2024.11.003
Ji-Ping Hou , Lian-Ying Yang , Li-Bin Liu , En-Kun Han , Chun-Qi Han , Li-Ping Yang
Background and study aims
This study was aimed to validate the correlation of circular RNA HIPK3 (CircHIPK3) expression in serum and tissues with the progression of liver fibrosis (LF) and liver cirrhosis (LC).
Patients and methods
Serum CircHIPK3 expressions were detected in 120 patients with LF/LC and 120 healthy controls (HCs). CircHIPK3 expression in tissues was detected in 120 fibrotic liver tissues and compared to 57 healthy liver tissues from patients with hepatic hemangioma. The expressions of CircHIPK3, TGF-β1, and CollA1 mRNAs were assessed by qRT-PCR. The Child-Pugh (CP) classification was used to evaluate disease severity. The Ishak score was applied to assess LF/LC in liver biopsy samples. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also investigated. Receiver operating characteristic (ROC) analysis was conducted to assess the diagnostic value of CircHIPK3 expressions in serum and tissues.
Results
CircHIPK3 expressions in serum and tissues were upregulated in patients with LF/LC compared to HCs. The patient group comprised 39 with CP class A (CP-A), 45 with CP class B (CP-B), and 36 with CP class B (CP-C). Patients with CP-C had markedly increased serum and local CircHIPK3 levels compared to those with CP-B and CP-A. Patients with CP-B showed upregulated CircHIPK3 expressions in serum and tissues compared to CP-A with statistical significance. ROC curve analysis indicated that CircHIPK3 expressions in both serum and tissues may serve as potential diagnostic indicators for the progression of LF/LC. Moreover, serum CircHIPK3 expressions were positively associated with serum ALT and AST levels. Tissue CircHIPK3 expressions were positively correlated with tissue TGF-β1 and CollA1 mRNA expressions. In addition, both serum and tissue CircHIPK3 expressions were positively associated with the Ishak score.
Conclusions
For the first time, this study demonstrated the positive correlation of CircHIPK3 expressions in both serum and tissues with the progression of LF/LC, regardless of etiology. CircHIPK3 might play a significant role in the development of LF/LC and act as a potential therapeutic target for these conditions.
{"title":"Correlation of local and serum CircHIPK3 expressions with the progression of liver fibrosis/cirrhosis","authors":"Ji-Ping Hou , Lian-Ying Yang , Li-Bin Liu , En-Kun Han , Chun-Qi Han , Li-Ping Yang","doi":"10.1016/j.ajg.2024.11.003","DOIUrl":"10.1016/j.ajg.2024.11.003","url":null,"abstract":"<div><h3>Background and study aims</h3><div>This study was aimed to validate the correlation of circular RNA HIPK3 (CircHIPK3) expression in serum and tissues with the progression of liver fibrosis (LF) and liver cirrhosis (LC).</div></div><div><h3>Patients and methods</h3><div>Serum CircHIPK3 expressions were detected in 120 patients with LF/LC and 120 healthy controls (HCs). CircHIPK3 expression in tissues was detected in 120 fibrotic liver tissues and compared to 57 healthy liver tissues from patients with hepatic hemangioma. The expressions of CircHIPK3, TGF-β1, and CollA1 mRNAs were assessed by qRT-PCR. The Child-Pugh (CP) classification was used to evaluate disease severity. The Ishak score was applied to assess LF/LC in liver biopsy samples. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also investigated. Receiver operating characteristic (ROC) analysis was conducted to assess the diagnostic value of CircHIPK3 expressions in serum and tissues.</div></div><div><h3>Results</h3><div>CircHIPK3 expressions in serum and tissues were upregulated in patients with LF/LC compared to HCs. The patient group comprised 39 with CP class A (CP-A), 45 with CP class B (CP-B), and 36 with CP class B (CP-C). Patients with CP-C had markedly increased serum and local CircHIPK3 levels compared to those with CP-B and CP-A. Patients with CP-B showed upregulated CircHIPK3 expressions in serum and tissues compared to CP-A with statistical significance. ROC curve analysis indicated that CircHIPK3 expressions in both serum and tissues may serve as potential diagnostic indicators for the progression of LF/LC. Moreover, serum CircHIPK3 expressions were positively associated with serum ALT and AST levels. Tissue CircHIPK3 expressions were positively correlated with tissue TGF-β1 and CollA1 mRNA expressions. In addition, both serum and tissue CircHIPK3 expressions were positively associated with the Ishak score.</div></div><div><h3>Conclusions</h3><div>For the first time, this study demonstrated the positive correlation of CircHIPK3 expressions in both serum and tissues with the progression of LF/LC, regardless of etiology. CircHIPK3 might play a significant role in the development of LF/LC and act as a potential therapeutic target for these conditions.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 71-77"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ajg.2025.01.003
Ahmad Moussawi , Abbas Karim , Don Rockey , Kassem Barada
{"title":"Prone positioning over a pillow and back pressure to facilitate colonoscopy completion in obese patients","authors":"Ahmad Moussawi , Abbas Karim , Don Rockey , Kassem Barada","doi":"10.1016/j.ajg.2025.01.003","DOIUrl":"10.1016/j.ajg.2025.01.003","url":null,"abstract":"","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 1-2"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ajg.2024.11.002
Ali Hajj Ali , Mohamad Ali Ibrahim , Ayman Alrazim, Yasser Shaib
Background
Mucosa-Associated Lymphoid Tissue (MALT) lymphoma or MALToma is a type of non-Hodgkin lymphoma arising in the gastric mucosa that has largely been associated with Helicobacter pylori (H. pylori) infection. However, less than 10% of gastric MALTomas can occur with a negative H. pylori status, and the disease seems to have a different course.
Patients and methods
Patients diagnosed with MALToma from 2000 to 2021 were included in the study. H. pylori-negative (HPN) status was confirmed when patients had at least 2 negative tests among the following: urea breath test, rapid urease test, serological test, or histology. The patients were divided into H. pylori positive (HPP) and HPN groups.
Results
The final analysis included 52 gastric MALToma patients, 25 (48.1 %) were HPN. Demographics and disease stages were comparable between the two groups, although a higher prevalence of HPN cases emerged in patients diagnosed from 2011 to 2021 compared to the 2000–2010 period (55.3 % vs. 28.6 %, p = 0.09). All patients in the HPP group received eradication therapy (ET) compared to only 40 % in the HPN group. ET success in the stage 1 HPN group was 25 % compared to 78.6 % in the HPP group (p = 0.03). More patients in the HPN group received chemo and/or radiotherapy compared to the HPP (86.4 % vs 57.1 %, p = 0.033). Treatment outcomes were similar between both groups. Comparing stage 1 MALToma patients who responded to ET versus non-responders revealed that responders were more likely to be HPP (76.8 % vs. 33.3 %, p = 0.026) and diagnosed in the earlier period (2000–2010, p = 0.048).
Conclusion
HPN MALToma patients were similar to HPP patients in clinical features. However, there was an increase in diagnosis of HPN MALToma and a decrease in response to ET in more recent years.
背景：粘膜相关淋巴组织（MALT）淋巴瘤或MALToma是一种发生在胃粘膜的非霍奇金淋巴瘤，主要与幽门螺杆菌（h.p ylori）感染有关。然而，只有不到10%的胃MALTomas可以在幽门螺杆菌阴性状态下发生，并且该疾病似乎有不同的病程。患者和方法：2000年至2021年诊断为MALToma的患者纳入研究。当患者在尿素呼气试验、快速脲酶试验、血清学试验或组织学试验中至少有2项阴性时，确认幽门螺杆菌阴性（HPN）状态。将患者分为幽门螺杆菌阳性（HPP）组和HPN组。结果：最终分析胃MALToma患者52例，HPN 25例（48.1%）。两组之间的人口统计学和疾病分期具有可比性，尽管2011年至2021年诊断的患者中HPN病例的患病率高于2000年至2010年期间（55.3%对28.6%,p = 0.09）。HPP组的所有患者都接受了根除治疗（ET），而HPN组只有40%。1期HPN组的ET成功率为25%，而HPP组为78.6% （p = 0.03）。与HPP组相比，HPN组更多的患者接受了化疗和/或放疗（86.4% vs 57.1%, p = 0.033）。两组治疗结果相似。比较对ET有反应的1期MALToma患者和无反应的患者发现，反应者更可能是HPP （76.8% vs 33.3%, p = 0.026）和早期诊断（2000-2010,p = 0.048）。结论：HPN MALToma患者的临床特征与HPP患者相似。然而，近年来，HPN MALToma的诊断有所增加，而对ET的反应有所减少。
{"title":"Clinical features and temporal trends in H. pylori negative gastric maltoma","authors":"Ali Hajj Ali , Mohamad Ali Ibrahim , Ayman Alrazim, Yasser Shaib","doi":"10.1016/j.ajg.2024.11.002","DOIUrl":"10.1016/j.ajg.2024.11.002","url":null,"abstract":"<div><h3>Background</h3><div>Mucosa-Associated Lymphoid Tissue (MALT) lymphoma or MALToma is a type of non-Hodgkin lymphoma arising in the gastric mucosa that has largely been associated with Helicobacter pylori (H. pylori) infection. However, less than 10% of gastric MALTomas can occur with a negative H. pylori status, and the disease seems to have a different course.</div></div><div><h3>Patients and methods</h3><div>Patients diagnosed with MALToma from 2000 to 2021 were included in the study. H. pylori-negative (HPN) status was confirmed when patients had at least 2 negative tests among the following: urea breath test, rapid urease test, serological test, or histology. The patients were divided into H. pylori positive (HPP) and HPN groups.</div></div><div><h3>Results</h3><div>The final analysis included 52 gastric MALToma patients, 25 (48.1 %) were HPN. Demographics and disease stages were comparable between the two groups, although a higher prevalence of HPN cases emerged in patients diagnosed from 2011 to 2021 compared to the 2000–2010 period (55.3 % vs. 28.6 %, p = 0.09). All patients in the HPP group received eradication therapy (ET) compared to only 40 % in the HPN group. ET success in the stage 1 HPN group was 25 % compared to 78.6 % in the HPP group (p = 0.03). More patients in the HPN group received chemo and/or radiotherapy compared to the HPP (86.4 % vs 57.1 %, p = 0.033). Treatment outcomes were similar between both groups. Comparing stage 1 MALToma patients who responded to ET versus non-responders revealed that responders were more likely to be HPP (76.8 % vs. 33.3 %, p = 0.026) and diagnosed in the earlier period (2000–2010, p = 0.048).</div></div><div><h3>Conclusion</h3><div>HPN MALToma patients were similar to HPP patients in clinical features. However, there was an increase in diagnosis of HPN MALToma and a decrease in response to ET in more recent years.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 67-70"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ajg.2025.01.008
Fatt Yang Chew , Pei-Hua Lee , Shu Wei Su , Suat Yee Lee
{"title":"Rigler’s triad of gallstone ileus","authors":"Fatt Yang Chew , Pei-Hua Lee , Shu Wei Su , Suat Yee Lee","doi":"10.1016/j.ajg.2025.01.008","DOIUrl":"10.1016/j.ajg.2025.01.008","url":null,"abstract":"","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 137-138"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.ajg.2024.07.005
Meng Jiang , Chang-li Li , Xing-chen Lin , Mei Hong , Huan-huan Li
Background and study aims
Hirschsprung disease (HD) is a complex developmental disease that resulted from impaired proliferation and migration of neural crest cells. Despite the genetic causation of enteric nervous system have been found to be responsible for part of HD cases, the genetic aetiology of most HD patients still needs to be explored.
Patients and methods
Whole-genome sequencing and subsequent Sanger sequencing validation analysis were performed in 13 HD children and their unaffected parents. Autophagy assays were performed to validate the functions of the identified locus.
Results
After the initial quality checking (SNP quality score ≥ 40, coverage ≥ 10X) of the raw data, we identified 3182 single nucleotide variants (SNVs). We subsequently compared these SNVs against the public databases and got a total of 15 suspicious genes shared among these patients. Subsequent Sanger sequencing and bioinformatics analyses revealed that amino acid–altering de novo mutation c.1648C > T(p.L550F) in ALK was responsible for HD. For validation, we sequenced all 29 exons of ALK in 76 additional sporadic HD cases and 200 healthy children and identified this variant in five of the HD cases. We further illustrated that ALK mutation c.1648C > T interrupted the interactions between ALK and its ligand midkine (Mdk), and induced autophagic cell death through AKT/mTORC1 axis.
Conclusion
These finding implied that the abnormal variant of ALK c.1648C > T may account for the pathogenesis of HD.
背景和研究目的赫氏胃肠病（HD）是一种复杂的发育性疾病，由神经嵴细胞增殖和迁移障碍引起。尽管已发现肠神经系统的遗传病因是部分 HD 病例的原因，但大多数 HD 患者的遗传病因仍有待探索。结果在对原始数据进行初步质量检查（SNP 质量得分≥ 40，覆盖率≥ 10X）后，我们确定了 3182 个单核苷酸变异（SNVs）。随后，我们将这些 SNV 与公共数据库进行了比对，发现这些患者共有 15 个可疑基因。随后的桑格测序和生物信息学分析表明，ALK中的c.1648C >T(p.L550F)氨基酸改变基因突变是导致HD的原因。为了进行验证，我们又对 76 例散发性 HD 病例和 200 例健康儿童的 ALK 全部 29 个外显子进行了测序，结果在 5 例 HD 病例中发现了这一变异。我们进一步证实，ALK c.1648C>T变异打断了ALK与其配体midkine（Mdk）之间的相互作用，并通过AKT/mTORC1轴诱导自噬性细胞死亡。
{"title":"Whole-genome sequencing identified ALK as a novel susceptible gene of Hirschsprung disease","authors":"Meng Jiang , Chang-li Li , Xing-chen Lin , Mei Hong , Huan-huan Li","doi":"10.1016/j.ajg.2024.07.005","DOIUrl":"10.1016/j.ajg.2024.07.005","url":null,"abstract":"<div><h3>Background and study aims</h3><div>Hirschsprung disease (HD) is a complex developmental disease that resulted from impaired proliferation and migration of neural crest cells. Despite the genetic causation of enteric nervous system have been found to be responsible for part of HD cases, the genetic aetiology of most HD patients still needs to be explored.</div></div><div><h3>Patients and methods</h3><div>Whole-genome sequencing and subsequent Sanger sequencing validation analysis were performed in 13 HD children and their unaffected parents. Autophagy assays were performed to validate the functions of the identified locus.</div></div><div><h3>Results</h3><div>After the initial quality checking (SNP quality score ≥ 40, coverage ≥ 10X) of the raw data, we identified 3182 single nucleotide variants (SNVs). We subsequently compared these SNVs against the public databases and got a total of 15 suspicious genes shared among these patients. Subsequent Sanger sequencing and bioinformatics analyses revealed that amino acid–altering de novo mutation c.1648C > T(p.L550F) in ALK was responsible for HD. For validation, we sequenced all 29 exons of<!--> <!-->ALK<!--> <!-->in 76 additional sporadic HD cases and 200 healthy children and identified this variant in five of the HD cases. We further illustrated that ALK mutation c.1648C > T interrupted the interactions between ALK and its ligand midkine (Mdk), and induced autophagic cell death through AKT/mTORC1 axis.</div></div><div><h3>Conclusion</h3><div>These finding implied that the abnormal variant of ALK c.1648C > T may account for the pathogenesis of HD.</div></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":"26 1","pages":"Pages 53-61"},"PeriodicalIF":1.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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