Hermansky-Pudlak syndrome (HPS) is a collection of autosomal recessive multisystemic disorders with at least 11 different types, categorized on the basis of involved genes. The disease is mostly characterized by tyrosinase-positive oculocutaneous albinism (OCA), platelet storage deficiency, absence of platelet dense bodies, and immune deficiency. Here we described a 2-month-old female infant with generalized hypotonia, recurrent infections, bilateral optic atrophy, nystagmus, cerebral atrophy, and elevated liver enzymes. Unlike her parents, she had chestnut colored hair, fair skin, and brown eyes. Parents had a consanguineous marriage, and their first child had died with similar symptoms at the age of 5 months. Whole exome sequencing (WES) was performed on DNA extracted from the patient's peripheral blood. Following the bioinformatics analysis, a likely pathogenic novel variant in the fifth exon of the BLOC1S6 gene (NM_001311255: c.506dupT: p. L169Ffs*33) was introduced by the Sadra Medical Genetic Laboratory. This variant was confirmed in the patient and segregated in both parents by Sanger sequencing.
This report presented the first congenital case of HPS-9 worldwide that might have led to early neonatal death. Our current patient shows new considerable features related to the BLOC1S6 gene variant and HPS-9, which is a valuable source for future research, prediction, clinical management, genetic counseling, and prenatal diagnosing.
赫尔曼斯基-普德拉克综合征（HPS）是一种常染色体隐性多系统疾病，根据涉及的基因分类，至少有 11 种不同类型。该病主要表现为酪氨酸酶阳性的眼皮肤白化病（OCA）、血小板储存缺乏症、血小板致密体缺失和免疫缺陷。本文描述了一名 2 个月大的女婴，她全身肌张力低下、反复感染、双侧视神经萎缩、眼球震颤、脑萎缩和肝酶升高。与父母不同，她有栗色的头发、白皙的皮肤和棕色的眼睛。她的父母是近亲结婚，他们的第一个孩子在5个月大时因类似症状夭折。对从患者外周血中提取的 DNA 进行了全外显子组测序（WES）。经过生物信息学分析，萨德拉医学遗传实验室在 BLOC1S6 基因的第五外显子上发现了一个可能致病的新型变异体（NM_001311255: c.506dupT: p. L169Ffs*33）。通过桑格测序，该变异在患者体内得到证实，并在患者父母中得到分离。该报告介绍了全球首例可能导致新生儿早期死亡的先天性 HPS-9 病例。我们的患者显示出了与 BLOC1S6 基因变异和 HPS-9 相关的新的重要特征，这对未来的研究、预测、临床管理、遗传咨询和产前诊断具有重要价值。
{"title":"A likely pathogenic homozygous frameshift variant in BLOC1S6 associated with a rare form of congenital Hermansky-Pudlak syndrome 9","authors":"Ahoura Nozari , Paria Babaahmadi , Anahita Farahzad Boroujeni , Roya Choopani , Taha Sadeghi , Korosh Heydari , Alireza Sadeghi","doi":"10.1016/j.genrep.2024.102086","DOIUrl":"10.1016/j.genrep.2024.102086","url":null,"abstract":"<div><div>Hermansky-Pudlak syndrome (HPS) is a collection of autosomal recessive multisystemic disorders with at least 11 different types, categorized on the basis of involved genes. The disease is mostly characterized by tyrosinase-positive oculocutaneous albinism (OCA), platelet storage deficiency, absence of platelet dense bodies, and immune deficiency. Here we described a 2-month-old female infant with generalized hypotonia, recurrent infections, bilateral optic atrophy, nystagmus, cerebral atrophy, and elevated liver enzymes. Unlike her parents, she had chestnut colored hair, fair skin, and brown eyes. Parents had a consanguineous marriage, and their first child had died with similar symptoms at the age of 5 months. Whole exome sequencing (WES) was performed on DNA extracted from the patient's peripheral blood. Following the bioinformatics analysis, a likely pathogenic novel variant in the fifth exon of the <em>BLOC1S6</em> gene (NM_001311255: c.506dupT: p. L169Ffs*33) was introduced by the Sadra Medical Genetic Laboratory. This variant was confirmed in the patient and segregated in both parents by Sanger sequencing.</div><div>This report presented the first congenital case of HPS-9 worldwide that might have led to early neonatal death. Our current patient shows new considerable features related to the <em>BLOC1S6</em> gene variant and HPS-9, which is a valuable source for future research, prediction, clinical management, genetic counseling, and prenatal diagnosing.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102086"},"PeriodicalIF":1.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650896","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}
<div><h3>Background</h3><div>Patients with COVID-19 have an increased risk of thrombosis and coagulopathy. Homocysteine, an amino acid essential to coagulation, is thought to be involved in such conditions, as its level is mediated by the presence of some single nucleotide polymorphisms (SNPs) in certain genes including <em>MTHFR</em>, <em>MTR</em> and <em>MTRR</em>.</div></div><div><h3>Aim</h3><div>The current study aimed to assess the significant role of <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G and <em>MTRR</em> A66G SNPs as risk factors for thrombosis among Egyptian COVID-19 patients and their effect on homocysteine level.</div></div><div><h3>Subjects and methods</h3><div>This case-control study was carried out on 90 Egyptian COVID-19 cases, divided into 45 non-complicated cases and 45 complicated cases with thrombosis, in addition to 80 healthy control individuals. DNA was isolated from blood samples of all the participants. The genotyping was performed using real-time PCR; in addition, serum homocysteine level was estimated.</div></div><div><h3>Results</h3><div>The <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G and <em>MTRR</em> A66G variants revealed a significant higher risk of thrombosis under different genetic models including the homozygous comparison of the co-dominant (20 % vs. 2.3 %, OR = 15.88, <em>p</em> = 0.007), the dominant (62.2 % vs. 33.3 % OR = 3.29, <em>p</em> = 0.006) and the allelic models (41.1 % vs. 17.8 %, OR = 3.2, <em>p</em> < 0.001) for <em>MTHFR</em> C677T and also the dominant (77.8 % vs. 51.1 %, OR = 3.3, <em>p</em> = 0.008) and the allelic models (52.2 % vs. 31.1 %, OR = 2.4, <em>p</em> = 0.004) for <em>MTHFR</em> A1298C. In addition, the heterozygous comparison of the co-dominant (60 vs. 11.1, OR = 12.7, <em>p</em> < 0.001), the dominant (62.2 % vs. 11.1 %, OR = 13.1, <em>p</em> < 0.001) and the allelic models (32.2 % vs. 5.6 %, OR = 8.08, <em>p</em> < 0.001) for <em>MTR</em> A2756G and the heterozygous and homozygous comparisons of the co-dominant model [(53.3 % vs. 31.1 %, OR = 3.4, <em>p</em> = 0.03) and (13.4 % vs. 2.2 %, OR = 12.0, <em>p</em> = 0.049), respectively], the dominant (66.4 % vs. 33.3 %, OR = 4.0, <em>p</em> = 0.001) and the allelic models (40 % vs. 17.8 %, OR = 3, <em>p</em> = 0.001) for <em>MTRR</em> A66G. Moreover, <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G, and <em>MTRR</em> A66G variants were also associated with high levels of serum homocysteine (<em>p</em> = 0.045, 0.001, 0.005 and 0.039, respectively). The homocysteine level was related to the disease severity by its correlation with higher LDH (rs = 0.49, <em>p</em> < 0.001), CRP (rs = 0.44, <em>p</em> < 0.001), IL-6 (rs = 0.46, <em>p</em> < 0.001) and D-dimer (rs = 0.66, <em>p</em> < 0.001) levels. The multivariate regression analysis showed that homocysteine and the dominant models of <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G and <em>MTRR</em> A66G were independent
{"title":"Association of thrombophilic genes (MTHFR, MTR and MTRR) polymorphisms and homocysteine level in relation to the increased risk of thrombosis among COVID-19 patients","authors":"Mohamed El-Ghonaimy , Mohamed El-Deeb , Shaimaa El-Ashwah , Manal Fouda , Menna Al-Adl , Ahmed EL-Sebaie","doi":"10.1016/j.genrep.2024.102085","DOIUrl":"10.1016/j.genrep.2024.102085","url":null,"abstract":"<div><h3>Background</h3><div>Patients with COVID-19 have an increased risk of thrombosis and coagulopathy. Homocysteine, an amino acid essential to coagulation, is thought to be involved in such conditions, as its level is mediated by the presence of some single nucleotide polymorphisms (SNPs) in certain genes including <em>MTHFR</em>, <em>MTR</em> and <em>MTRR</em>.</div></div><div><h3>Aim</h3><div>The current study aimed to assess the significant role of <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G and <em>MTRR</em> A66G SNPs as risk factors for thrombosis among Egyptian COVID-19 patients and their effect on homocysteine level.</div></div><div><h3>Subjects and methods</h3><div>This case-control study was carried out on 90 Egyptian COVID-19 cases, divided into 45 non-complicated cases and 45 complicated cases with thrombosis, in addition to 80 healthy control individuals. DNA was isolated from blood samples of all the participants. The genotyping was performed using real-time PCR; in addition, serum homocysteine level was estimated.</div></div><div><h3>Results</h3><div>The <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G and <em>MTRR</em> A66G variants revealed a significant higher risk of thrombosis under different genetic models including the homozygous comparison of the co-dominant (20 % vs. 2.3 %, OR = 15.88, <em>p</em> = 0.007), the dominant (62.2 % vs. 33.3 % OR = 3.29, <em>p</em> = 0.006) and the allelic models (41.1 % vs. 17.8 %, OR = 3.2, <em>p</em> < 0.001) for <em>MTHFR</em> C677T and also the dominant (77.8 % vs. 51.1 %, OR = 3.3, <em>p</em> = 0.008) and the allelic models (52.2 % vs. 31.1 %, OR = 2.4, <em>p</em> = 0.004) for <em>MTHFR</em> A1298C. In addition, the heterozygous comparison of the co-dominant (60 vs. 11.1, OR = 12.7, <em>p</em> < 0.001), the dominant (62.2 % vs. 11.1 %, OR = 13.1, <em>p</em> < 0.001) and the allelic models (32.2 % vs. 5.6 %, OR = 8.08, <em>p</em> < 0.001) for <em>MTR</em> A2756G and the heterozygous and homozygous comparisons of the co-dominant model [(53.3 % vs. 31.1 %, OR = 3.4, <em>p</em> = 0.03) and (13.4 % vs. 2.2 %, OR = 12.0, <em>p</em> = 0.049), respectively], the dominant (66.4 % vs. 33.3 %, OR = 4.0, <em>p</em> = 0.001) and the allelic models (40 % vs. 17.8 %, OR = 3, <em>p</em> = 0.001) for <em>MTRR</em> A66G. Moreover, <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G, and <em>MTRR</em> A66G variants were also associated with high levels of serum homocysteine (<em>p</em> = 0.045, 0.001, 0.005 and 0.039, respectively). The homocysteine level was related to the disease severity by its correlation with higher LDH (rs = 0.49, <em>p</em> < 0.001), CRP (rs = 0.44, <em>p</em> < 0.001), IL-6 (rs = 0.46, <em>p</em> < 0.001) and D-dimer (rs = 0.66, <em>p</em> < 0.001) levels. The multivariate regression analysis showed that homocysteine and the dominant models of <em>MTHFR</em> (C677T and A1298C), <em>MTR</em> A2756G and <em>MTRR</em> A66G were independent","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102085"},"PeriodicalIF":1.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650897","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 : 2024-11-08DOI: 10.1016/j.genrep.2024.102084
Saheli Bose , Nirmalya Dey
Dysregulated physiological pathways are a hallmark of metabolic syndromes and often act as cancer risk factors. MicroRNAs (miRNAs) have become important regulators of many biological processes, including growth, development and metabolism. MicroRNAs often play a dual role in metabolic syndromes and cancer development through the modulation of pathways that affect cell proliferation, energy balance, and cellular stress responses. Obesity, insulin resistance, type 2 Diabetes, cardiovascular diseases, hypertension, dyslipidemia do always remain ‘list toppers’ since the inception of the concept of ‘metabolic syndrome’. Aberrantly expressed miRNAs exhibit to play a pivotal role in disturbed metabolic pathways, chronic inflammation, and oxidative stress rendering people predisposed to these metabolic disorders. MicroRNAs can diagnose and predict outcomes in various pathophysiological instances. Hence, miRNA profiles can act as biomarkers for early illness diagnosis, disease progression, and treatment response. The complex crosstalk between different metabolic pathways may be managed by using miRNAs as therapeutic targets or tools for precision medicine. The current review focuses on elaborating the complex functions played by miRNAs in bridging the gap between the unexplored areas of metabolic syndromes, keeping cancer off this discussion.
{"title":"MicroRNAs: Tiny biomolecules with soaring impact in regulation of metabolic syndrome","authors":"Saheli Bose , Nirmalya Dey","doi":"10.1016/j.genrep.2024.102084","DOIUrl":"10.1016/j.genrep.2024.102084","url":null,"abstract":"<div><div>Dysregulated physiological pathways are a hallmark of metabolic syndromes and often act as cancer risk factors. MicroRNAs (miRNAs) have become important regulators of many biological processes, including growth, development and metabolism. MicroRNAs often play a dual role in metabolic syndromes and cancer development through the modulation of pathways that affect cell proliferation, energy balance, and cellular stress responses. Obesity, insulin resistance, type 2 Diabetes, cardiovascular diseases, hypertension, dyslipidemia do always remain ‘list toppers’ since the inception of the concept of ‘metabolic syndrome’. Aberrantly expressed miRNAs exhibit to play a pivotal role in disturbed metabolic pathways, chronic inflammation, and oxidative stress rendering people predisposed to these metabolic disorders. MicroRNAs can diagnose and predict outcomes in various pathophysiological instances. Hence, miRNA profiles can act as biomarkers for early illness diagnosis, disease progression, and treatment response. The complex crosstalk between different metabolic pathways may be managed by using miRNAs as therapeutic targets or tools for precision medicine. The current review focuses on elaborating the complex functions played by miRNAs in bridging the gap between the unexplored areas of metabolic syndromes, keeping cancer off this discussion.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102084"},"PeriodicalIF":1.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650895","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 : 2024-11-07DOI: 10.1016/j.genrep.2024.102083
Veera Krishna Goud , Alladi Charanraj Goud , Sivaranjini Ramassamy , M. Jayanthi , R. Medha , Laxmisha Chandrashekar
Background
Psoriasis is a chronic inflammatory skin disease characterised by hyperproliferation of keratinocytes and abnormal immune response. It manifests in genetically predisposed individuals exposed to environmental triggers like infections, drugs, stress, and trauma. Epigenetic mechanisms are a critical component of the complex etiopathogenesis of psoriasis, as they modulate gene expression and increase disease risk. There are many conflicting reports regarding DNA methylation in patients with psoriasis. This could well reflect the choice of tissue and technique used. Data on whole blood DNA methylation in psoriasis is sparse.
Objective
The present study aims to measure the levels of DNA methylation [5-methylcytosine (5-mC)] in psoriatic patients from whole blood pre and post-treatment with methotrexate and its correlation with disease severity.
Methods
We recruited thirty cases of psoriasis vulgaris and 30 healthy controls. Thirty psoriatic patients were on methotrexate treatment and followed up for three months. 5-methylcytosine was measured using a global DNA methylation ELISA kit.
Results
The 5-methylcytosine levels from whole blood DNA were 8.13±1.89 % in cases and 5.37±2.33 % in controls, which was statistically significant (p = 0.0001). Post-treatment with methotrexate, there was a significant reduction (p = 0.0001) in the 5-methylcytosine levels in cases (4.54±1.74 %). Pre and post-treatment 5-methylcytosine levels were not significantly associated with the Psoriasis Area Severity Index (PASI) score.
Conclusion
Patients with psoriasis have whole-blood DNA global hypermethylation. Treatment with methotrexate leads to a significant reduction in DNA hypermethylation.
背景银屑病是一种慢性炎症性皮肤病，以角质细胞过度增殖和异常免疫反应为特征。它主要发生在易受感染、药物、压力和创伤等环境诱因影响的遗传易感人群中。表观遗传机制是银屑病复杂发病机制的重要组成部分，因为它们会调节基因表达并增加患病风险。关于银屑病患者的 DNA 甲基化，有许多相互矛盾的报道。这很可能反映了所选择的组织和所使用的技术。本研究旨在测量甲氨蝶呤治疗前后银屑病患者全血中 DNA 甲基化[5-甲基胞嘧啶（5-mC）]的水平及其与疾病严重程度的相关性。30 名银屑病患者接受了甲氨蝶呤治疗，并随访了三个月。结果病例全血DNA中的5-甲基胞嘧啶含量为8.13±1.89%，对照组为5.37±2.33%，差异有统计学意义（P = 0.0001）。甲氨蝶呤治疗后，病例的 5-甲基胞嘧啶水平（4.54±1.74 %）明显下降（p = 0.0001）。治疗前和治疗后的 5-甲基胞嘧啶水平与银屑病面积严重程度指数（PASI）评分无明显关联。结论银屑病患者的全血DNA整体高甲基化，甲氨蝶呤治疗可显著降低DNA高甲基化。
{"title":"Whole blood global DNA methylation [5-methylcytosine (5-mC)] levels in psoriatic patients before and after methotrexate treatment","authors":"Veera Krishna Goud , Alladi Charanraj Goud , Sivaranjini Ramassamy , M. Jayanthi , R. Medha , Laxmisha Chandrashekar","doi":"10.1016/j.genrep.2024.102083","DOIUrl":"10.1016/j.genrep.2024.102083","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis is a chronic inflammatory skin disease characterised by hyperproliferation of keratinocytes and abnormal immune response. It manifests in genetically predisposed individuals exposed to environmental triggers like infections, drugs, stress, and trauma. Epigenetic mechanisms are a critical component of the complex etiopathogenesis of psoriasis, as they modulate gene expression and increase disease risk. There are many conflicting reports regarding DNA methylation in patients with psoriasis. This could well reflect the choice of tissue and technique used. Data on whole blood DNA methylation in psoriasis is sparse.</div></div><div><h3>Objective</h3><div>The present study aims to measure the levels of DNA methylation [5-methylcytosine (5-mC)] in psoriatic patients from whole blood pre and post-treatment with methotrexate and its correlation with disease severity.</div></div><div><h3>Methods</h3><div>We recruited thirty cases of psoriasis vulgaris and 30 healthy controls. Thirty psoriatic patients were on methotrexate treatment and followed up for three months. 5-methylcytosine was measured using a global DNA methylation ELISA kit.</div></div><div><h3>Results</h3><div>The 5-methylcytosine levels from whole blood DNA were 8.13±1.89 % in cases and 5.37±2.33 % in controls, which was statistically significant (<em>p</em> = 0.0001). Post-treatment with methotrexate, there was a significant reduction (p = 0.0001) in the 5-methylcytosine levels in cases (4.54±1.74 %). Pre and post-treatment 5-methylcytosine levels were not significantly associated with the Psoriasis Area Severity Index (PASI) score.</div></div><div><h3>Conclusion</h3><div>Patients with psoriasis have whole-blood DNA global hypermethylation. Treatment with methotrexate leads to a significant reduction in DNA hypermethylation.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102083"},"PeriodicalIF":1.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650893","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 : 2024-11-06DOI: 10.1016/j.genrep.2024.102080
Jin Changyu , Hu Huijie , Li Qingqing , Lai Yanli , Wang Jiaping , Mu Qitian , Ouyang Guifang , Sheng Lixia
In patients with recurrent anemia, jaundice, and splenomegaly, a thorough assessment of family history and peripheral blood smears is crucial for diagnosing hereditary spherocytosis (HS). Furthermore, gene sequencing can enhance diagnostic accuracy and facilitate the investigation of disease mechanisms at the molecular level. In this report, we present a case of HS caused by a heterozygous nonsense mutation in the SPTB gene, along with a family history of this specific mutation. A 35-year-old man was evaluated for jaundice and splenomegaly, which he had experienced since childhood. Blood tests revealed anemia, reticulocytosis, elevated indirect bilirubin levels, and an increased percentage of spherical red blood cells in the peripheral blood. His family history indicated that both his father and daughter exhibited similar clinical manifestations. Subsequently, genetic sequencing confirmed that the patient, along with his father and daughter, shared the heterozygous missense mutation c.155G > A (p.Arg52Gln) in the SPTB gene, which is absent in public population and animal sequence databases. Structural prediction analysis of the protein suggests that this mutation may lead to instability of SPTB mRNA, thereby affecting the synthesis of the spectrin protein and the integrity of the red blood cell membrane skeleton. Further research is needed to clarify the exact relationship between this mutation and the occurrence of HS.
{"title":"New mutation in the β-spectrin gene in hereditary spherocytosis: A case report","authors":"Jin Changyu , Hu Huijie , Li Qingqing , Lai Yanli , Wang Jiaping , Mu Qitian , Ouyang Guifang , Sheng Lixia","doi":"10.1016/j.genrep.2024.102080","DOIUrl":"10.1016/j.genrep.2024.102080","url":null,"abstract":"<div><div>In patients with recurrent anemia, jaundice, and splenomegaly, a thorough assessment of family history and peripheral blood smears is crucial for diagnosing hereditary spherocytosis (HS). Furthermore, gene sequencing can enhance diagnostic accuracy and facilitate the investigation of disease mechanisms at the molecular level. In this report, we present a case of HS caused by a heterozygous nonsense mutation in the SPTB gene, along with a family history of this specific mutation. A 35-year-old man was evaluated for jaundice and splenomegaly, which he had experienced since childhood. Blood tests revealed anemia, reticulocytosis, elevated indirect bilirubin levels, and an increased percentage of spherical red blood cells in the peripheral blood. His family history indicated that both his father and daughter exhibited similar clinical manifestations. Subsequently, genetic sequencing confirmed that the patient, along with his father and daughter, shared the heterozygous missense mutation c.155G > A (p.Arg52Gln) in the SPTB gene, which is absent in public population and animal sequence databases. Structural prediction analysis of the protein suggests that this mutation may lead to instability of SPTB mRNA, thereby affecting the synthesis of the spectrin protein and the integrity of the red blood cell membrane skeleton. Further research is needed to clarify the exact relationship between this mutation and the occurrence of HS.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102080"},"PeriodicalIF":1.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142651479","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 : 2024-11-01DOI: 10.1016/j.genrep.2024.102078
Isis Samy Bedira , Ibrahim El Tantawy El Sayed , Olfat M. Hendy , Mohamed Abdel-Samiee , Amany Mohamed Rashad , Ahmed B. Zaid
Background
HNF1A gene variants have been reported to be involved in developing mature onset diabetes mellitus (DM). Many studies reported the role of DM as a risk factor for hepatocellular carcinoma (HCC) development. To date, it has not been reported whether HNF1A gene variants are associated with the risk of DM in cirrhotic patients and their subsequent HCC.
Objective
To evaluate the HNF1A (the hepatocyte nuclear factor 1 homeobox A) genetic variants as a cofactor with DM for HCC development in hepatitis C virus (HCV)-infected patients.
Subjects and methods
This study was conducted on 140 subjects; 30 had HCC without DM, 30 HCC with DM, and 40 patients had DM with no HCV infection or had HCC; in addition, 80 healthy volunteers with matched ages and genders were enrolled in the study as a control group. Liver function tests, hepatitis viral markers, alpha-fetoprotein (AFP), fasting sugar and HBA1c and HNF1A (rs2464196 and rs1169310) using real-time polymerase chain reaction (PCR) were done for all participants.
Results
The frequency of HNF1A rs2464196 (AA) genotype in patient groups (DM, HCC, HCC + DM) was significantly higher compared to the control group (P = 0.006, P = 0.018, P < 0.001 respectively). The combined dominant model (AA + GA) of rs 2464196 was significantly higher than the (GG) genotype in patient groups (DM, HCC, HCC + DM) than the control group. In addition, the frequency of the AA genotype is more prevalent in HCC + DM (73 %) compared to the group of DM or HCC patients. In contrast, the HNF1A rs1169310 (TT, TC or CC genotypes) showed no significant difference among the four studied groups and their T or C allele distributions.
Conclusion
This finding suggested that the HNF1A rs2464196 (AA) genotype could be associated with DM and may raise the possibility of HCC development among HCV-infected patients who harbour this genotype more than (GG). On the contrary, the HNF1A rs1169310 polymorphism was of no significance as a risk factor in the current study. However, as we limited our study to Egyptian participants, more research on other ethnic groups would be required. Also, large scale studies are recommended on other variants of HNF1A to clarify the role of this gene in HCC development.
{"title":"Hepatocyte nuclear factor 1 alpha variants as risk factor for hepatocellular carcinoma development with and without diabetes mellitus","authors":"Isis Samy Bedira , Ibrahim El Tantawy El Sayed , Olfat M. Hendy , Mohamed Abdel-Samiee , Amany Mohamed Rashad , Ahmed B. Zaid","doi":"10.1016/j.genrep.2024.102078","DOIUrl":"10.1016/j.genrep.2024.102078","url":null,"abstract":"<div><h3>Background</h3><div>HNF1A gene variants have been reported to be involved in developing mature onset diabetes mellitus (DM). Many studies reported the role of DM as a risk factor for hepatocellular carcinoma (HCC) development. To date, it has not been reported whether HNF1A gene variants are associated with the risk of DM in cirrhotic patients and their subsequent HCC.</div></div><div><h3>Objective</h3><div>To evaluate the HNF1A (the hepatocyte nuclear factor 1 homeobox A) genetic variants as a cofactor with DM for HCC development in hepatitis C virus (HCV)-infected patients.</div></div><div><h3>Subjects and methods</h3><div>This study was conducted on 140 subjects; 30 had HCC without DM, 30 HCC with DM, and 40 patients had DM with no HCV infection or had HCC; in addition, 80 healthy volunteers with matched ages and genders were enrolled in the study as a control group. Liver function tests, hepatitis viral markers, alpha-fetoprotein (AFP), fasting sugar and HBA1c and HNF1A (rs2464196 and rs1169310) using real-time polymerase chain reaction (PCR) were done for all participants.</div></div><div><h3>Results</h3><div>The frequency of HNF1A rs2464196 (AA) genotype in patient groups (DM, HCC, HCC + DM) was significantly higher compared to the control group (<em>P</em> = 0.006, <em>P</em> = 0.018, <em>P</em> < 0.001 respectively). The combined dominant model (AA + GA) of rs 2464196 was significantly higher than the (GG) genotype in patient groups (DM, HCC, HCC + DM) than the control group. In addition, the frequency of the AA genotype is more prevalent in HCC + DM (73 %) compared to the group of DM or HCC patients. In contrast, the HNF1A rs1169310 (TT, TC or CC genotypes) showed no significant difference among the four studied groups and their T or C allele distributions.</div></div><div><h3>Conclusion</h3><div>This finding suggested that the HNF1A rs2464196 (AA) genotype could be associated with DM and may raise the possibility of HCC development among HCV-infected patients who harbour this genotype more than (GG). On the contrary, the HNF1A rs1169310 polymorphism was of no significance as a risk factor in the current study. However, as we limited our study to Egyptian participants, more research on other ethnic groups would be required. Also, large scale studies are recommended on other variants of HNF1A to clarify the role of this gene in HCC development.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102078"},"PeriodicalIF":1.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650894","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 : 2024-11-01DOI: 10.1016/j.genrep.2024.102079
Joel Henrique Ellwanger, José Artur Bogo Chies
Growing evidence suggests that tattoos may be associated with an increased risk of cancer development due to carcinogenic components present in tattoo inks. We explored this issue using The Comparative Toxicogenomics Database. Exploratory toxicogenomic data corroborate the association between cancer and tattoo ink components, especially concerning the effects of polycyclic aromatic hydrocarbons (PAH). The top-15 genes affected by PAH and the top-15 diseases associated with PAH were listed. Polycyclic aromatic hydrocarbons and other components present in tattoo inks affect the expression of multiple genes that participate in the metabolism of xenobiotics, cell death, and immune responses, and disruption of these processes may facilitate carcinogenesis. In agreement, cancer is the main disease category associated with PAH. In Brazil and other countries, there are significant deficiencies in the regulation, marketing, and inspection of substances used in tattoo inks. Considering the immense number of individuals who get tattoos around the world, tattoo inks should be subjected to more complete toxicological studies, and stricter regulation of tattoo ink usage is needed.
{"title":"Toxicogenomics supports carcinogenic action of tattoo ink components","authors":"Joel Henrique Ellwanger, José Artur Bogo Chies","doi":"10.1016/j.genrep.2024.102079","DOIUrl":"10.1016/j.genrep.2024.102079","url":null,"abstract":"<div><div>Growing evidence suggests that tattoos may be associated with an increased risk of cancer development due to carcinogenic components present in tattoo inks. We explored this issue using The Comparative Toxicogenomics Database. Exploratory toxicogenomic data corroborate the association between cancer and tattoo ink components, especially concerning the effects of polycyclic aromatic hydrocarbons (PAH). The top-15 genes affected by PAH and the top-15 diseases associated with PAH were listed. Polycyclic aromatic hydrocarbons and other components present in tattoo inks affect the expression of multiple genes that participate in the metabolism of xenobiotics, cell death, and immune responses, and disruption of these processes may facilitate carcinogenesis. In agreement, cancer is the main disease category associated with PAH. In Brazil and other countries, there are significant deficiencies in the regulation, marketing, and inspection of substances used in tattoo inks. Considering the immense number of individuals who get tattoos around the world, tattoo inks should be subjected to more complete toxicological studies, and stricter regulation of tattoo ink usage is needed.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102079"},"PeriodicalIF":1.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587268","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}
Phosphorus (P) deficiency hinders crop productivity of 50 % of the rice grown in Asia, Africa, and South America. About 90 % of the phosphate in fertilizers applied to the crops gets fixed in the soil, reducing its availability to plants. This necessitates increased use of phosphatic fertilizers leading to higher cost of cultivation and environmental pollution. Although molecular mechanisms of P-deficiency tolerance in rice are being deciphered, the role of transposable elements (TEs) in transcriptional reprogramming under P-starvation/deficiency stress has not yet been reported. To investigate the role of Pup1 QTL in controlling TE-mediated reprogramming of gene expression, a pair of contrasting rice [Pusa-44 and its Near-Isogenic Line (NIL)-23] genotypes were grown hydroponically under control and stressed (0 ppm Pi) conditions. Comparative RNA-seq analysis of root and shoot tissues from 45-day-old plants of the rice genotypes revealed TE-mediated transcriptional reprogramming affecting biological processes and cellular components. Significantly up-regulated expression of several TEs under P-starvation stress, controlled by Pup1 QTL, particularly in shoots of NIL-23 indicates their crucial role in P homeostasis. Moreover, comparative physio-biochemical analyses confirmed the stress tolerance of NIL-23. Several biological processes including DNA replication/repair, metabolism, signaling, and phosphorylation were modulated through differential (mainly up-regulated) expression of TEs (controlled by Pup1 QTL) in shoots of NIL-23 under P-starvation. To the best of our knowledge, this is a pioneer study on the role of TEs in reprogramming biological processes/molecular functions/cellular components involved in P-use efficiency in rice under stress. The findings advance our understanding of the functions of Pup1 to improve the P-use efficiency/productivity of rice in P-deficient soils.
{"title":"Comparative RNA-seq analysis reveals transposable element-mediated transcriptional reprogramming under phosphorus-starvation stress in rice (Oryza sativa L.)","authors":"Simardeep Kaur , Karishma Seem , K.K. Vinod , Dwijesh Chandra Mishra , Suresh Kumar , Trilochan Mohapatra","doi":"10.1016/j.genrep.2024.102077","DOIUrl":"10.1016/j.genrep.2024.102077","url":null,"abstract":"<div><div>Phosphorus (P) deficiency hinders crop productivity of 50 % of the rice grown in Asia, Africa, and South America. About 90 % of the phosphate in fertilizers applied to the crops gets fixed in the soil, reducing its availability to plants. This necessitates increased use of phosphatic fertilizers leading to higher cost of cultivation and environmental pollution. Although molecular mechanisms of P-deficiency tolerance in rice are being deciphered, the role of transposable elements (TEs) in transcriptional reprogramming under P-starvation/deficiency stress has not yet been reported. To investigate the role of <em>Pup1</em> QTL in controlling TE-mediated reprogramming of gene expression, a pair of contrasting rice [Pusa-44 and its Near-Isogenic Line (NIL)-23] genotypes were grown hydroponically under control and stressed (0 ppm Pi) conditions. Comparative RNA-seq analysis of root and shoot tissues from 45-day-old plants of the rice genotypes revealed TE-mediated transcriptional reprogramming affecting biological processes and cellular components. Significantly up-regulated expression of several TEs under P-starvation stress, controlled by <em>Pup1</em> QTL, particularly in shoots of NIL-23 indicates their crucial role in P homeostasis. Moreover, comparative physio-biochemical analyses confirmed the stress tolerance of NIL-23. Several biological processes including DNA replication/repair, metabolism, signaling, and phosphorylation were modulated through differential (mainly up-regulated) expression of TEs (controlled by <em>Pup1</em> QTL) in shoots of NIL-23 under P-starvation. To the best of our knowledge, this is a pioneer study on the role of TEs in reprogramming biological processes/molecular functions/cellular components involved in P-use efficiency in rice under stress. The findings advance our understanding of the functions of <em>Pup1</em> to improve the P-use efficiency/productivity of rice in P-deficient soils.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102077"},"PeriodicalIF":1.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573481","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 : 2024-10-31DOI: 10.1016/j.genrep.2024.102076
Rajender Goud Arolla , K. Srinivas Naik
Microalgae, a diverse class of photosynthetic eukaryote, can provide food and energy sustainably. Selecting productive strains is crucial for commercial viability. Here, we isolated an axenic microalgal species from Musi River water, and based on its morphology, molecular makeup, and cell wall composition identified it as Chlorella sp. CH2018. Scanning electron microscopy was used to measure the size of cells, which were found to be 3-, 4-, or 5-μm in diameter with a discernible thick outer cell wall. The characterization of algal genomes is imperative for comprehending species, studying metabolic pathways, and modifying genetics. In this study, we sequenced the entire genome of Chlorella sp. CH2018, yielded genome size of 56.83 Mb with 11,143 functionally annotated protein-coding gene models. The Gene Ontology (GO) analysis revealed that Chlorella's predominant metabolic pathway is carbohydrate metabolism. Ortholog comparative analysis of species of phylum Chlorophyta with Chlorella sp. CH2018 showed that the isolated species possesses unique protein families with a maximum number of 6292 ortholog groups with Chlorella sorokiniana. The phylogenetic tree created by concatenating single-copy ortholog sequences demonstrates the uniqueness of Chlorella sp. CH2018, and its genome sequence serves as a genetic resource for future research.
{"title":"Genomic characterization and comparative genomics of Chlorella sp. CH2018 from Musi River water, India","authors":"Rajender Goud Arolla , K. Srinivas Naik","doi":"10.1016/j.genrep.2024.102076","DOIUrl":"10.1016/j.genrep.2024.102076","url":null,"abstract":"<div><div>Microalgae, a diverse class of photosynthetic eukaryote, can provide food and energy sustainably. Selecting productive strains is crucial for commercial viability. Here, we isolated an axenic microalgal species from Musi River water, and based on its morphology, molecular makeup, and cell wall composition identified it as <em>Chlorella</em> sp. CH2018. Scanning electron microscopy was used to measure the size of cells, which were found to be 3-, 4-, or 5-μm in diameter with a discernible thick outer cell wall. The characterization of algal genomes is imperative for comprehending species, studying metabolic pathways, and modifying genetics. In this study, we sequenced the entire genome of <em>Chlorella</em> sp. CH2018, yielded genome size of 56.83 Mb with 11,143 functionally annotated protein-coding gene models. The Gene Ontology (GO) analysis revealed that <em>Chlorella</em>'s predominant metabolic pathway is carbohydrate metabolism. Ortholog comparative analysis of species of phylum Chlorophyta with <em>Chlorella</em> sp. CH2018 showed that the isolated species possesses unique protein families with a maximum number of 6292 ortholog groups with <em>Chlorella sorokiniana</em>. The phylogenetic tree created by concatenating single-copy ortholog sequences demonstrates the uniqueness of <em>Chlorella</em> sp. CH2018, and its genome sequence serves as a genetic resource for future research.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102076"},"PeriodicalIF":1.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587267","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 : 2024-10-30DOI: 10.1016/j.genrep.2024.102074
Hima J. Challa, Kalyan Ram Uppaluri, A.Sai. Rishika Gopikar, Rebecca Chalcedony, Srinivas Kethavath, K. Sri Manjari, K. Krishna Vardhani, Kalyani Palasamudram, Natya Kanuri, Aswini Korivepi
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by several environmental and genetic factors. We present a case of a 7-year-old male with ASD, neurogenic voiding dysfunction (NVD), speech and developmental delays, and hyperactivity, and current treatment includes speech, occupational, and behavioral therapy. Family history includes consanguinity and maternal intellectual disability. Whole-exome sequencing (WES) identified maternally inherited variants in CHD8 (benign), KMT2C (likely pathogenic), and EP300 and TCF4 (uncertain significance). Despite the benign classification of the CHD8 variant, its association with ASD highlights the complexity of genotype-phenotype correlations. The likely pathogenic KMT2C frameshift mutation and deletions in EP300 and TCF4 suggest a multifactorial genetic basis for ASD in this patient. These findings highlight the importance of integrating clinical and genetic data for accurate diagnosis and personalized treatment. Whole Exome Sequencing (WES) analysis revealed these variants in the child's mother, uncle, and maternal grandfather, with the maternal uncle unaffected by ASD, ID, or ADHD, indicating potential variant interplay in disease manifestation. This case emphasizes the need for further research to elucidate the combined effects of these variants, enhancing our understanding of ASD's genetic landscape and improving clinical outcomes.
{"title":"A case report on genetic variants in CHD8, KMT2C, EP300, and TCF4 associated with autism spectrum disorder","authors":"Hima J. Challa, Kalyan Ram Uppaluri, A.Sai. Rishika Gopikar, Rebecca Chalcedony, Srinivas Kethavath, K. Sri Manjari, K. Krishna Vardhani, Kalyani Palasamudram, Natya Kanuri, Aswini Korivepi","doi":"10.1016/j.genrep.2024.102074","DOIUrl":"10.1016/j.genrep.2024.102074","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition influenced by several environmental and genetic factors. We present a case of a 7-year-old male with ASD, neurogenic voiding dysfunction (NVD), speech and developmental delays, and hyperactivity, and current treatment includes speech, occupational, and behavioral therapy. Family history includes consanguinity and maternal intellectual disability. Whole-exome sequencing (WES) identified maternally inherited variants in <em>CHD8</em> (benign), <em>KMT2C</em> (likely pathogenic), and <em>EP300 and TCF4</em> (uncertain significance). Despite the benign classification of the <em>CHD8</em> variant, its association with ASD highlights the complexity of genotype-phenotype correlations. The likely pathogenic <em>KMT2C</em> frameshift mutation and deletions in <em>EP300 and TCF4</em> suggest a multifactorial genetic basis for ASD in this patient. These findings highlight the importance of integrating clinical and genetic data for accurate diagnosis and personalized treatment. Whole Exome Sequencing (WES) analysis revealed these variants in the child's mother, uncle, and maternal grandfather, with the maternal uncle unaffected by ASD, ID, or ADHD, indicating potential variant interplay in disease manifestation. This case emphasizes the need for further research to elucidate the combined effects of these variants, enhancing our understanding of ASD's genetic landscape and improving clinical outcomes.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"37 ","pages":"Article 102074"},"PeriodicalIF":1.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142573482","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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