Pub Date : 2024-03-12DOI: 10.1186/s43042-024-00502-9
Natalia Osinovskaya, Elena Vashukova, Olga Tarasenko, Maria Danilova, Olga Glavnova, Iskender Sultanov, Maxim Donnikov, Yulia Nasykhova, Andrey Glotov
21-hydroxylase deficiency is present in 90–95% of cases of congenital adrenal hyperplasia (CAH). Eleven major pathogenic variants account for 93% of all identified variants in the CYP21A2 gene in various clinical forms of the disease. Each population has its own range of significant pathogenic variants. We aimed to study the frequency of pathogenic variants in the CYP21A2 gene using NGS technology and real-time PCR in Surgut patients with different clinical forms of CAH. NGS was performed on 70 patients with salt-wasting and non-classical clinical forms of 21-hydroxylase deficiency, verified by direct Sanger sequencing and PCR–RFLP analysis. Eleven different pathogenic variants were found in 68.57% (48/70) of patients. Among 92.86% (13/14) of patients with salt-wasting CAH, variants were found to be homozygous, with CYP21A2 gene deletion as the most frequent mutation (46.4% or 13/28 alleles). In the group with non-classical CAH, pathogenic variants were identified only in 60.71% (34/56) of patients. V282L was discovered to be the most common variant in heterozygous carriers (45.45%, 15/33). NGS method identified 2 variants that were not determined by the standard method for major mutations detection: p.C170* and p.W22X, accounting for 3% of all known pathogenic variants. Our data make it possible to clarify the specific spectrum of CYP21A2 gene pathogenic variants in CAH patients from Surgut. The NGS method allows for the identification of rare pathogenic variants (3%) in the CYP21A2 gene that are not included in the conventional PCR–RFLP analysis.
{"title":"Analysis of the CYP21A2 gene pathogenic variants in CAH patients from Surgut using next-generation sequencing (NGS)","authors":"Natalia Osinovskaya, Elena Vashukova, Olga Tarasenko, Maria Danilova, Olga Glavnova, Iskender Sultanov, Maxim Donnikov, Yulia Nasykhova, Andrey Glotov","doi":"10.1186/s43042-024-00502-9","DOIUrl":"https://doi.org/10.1186/s43042-024-00502-9","url":null,"abstract":"21-hydroxylase deficiency is present in 90–95% of cases of congenital adrenal hyperplasia (CAH). Eleven major pathogenic variants account for 93% of all identified variants in the CYP21A2 gene in various clinical forms of the disease. Each population has its own range of significant pathogenic variants. We aimed to study the frequency of pathogenic variants in the CYP21A2 gene using NGS technology and real-time PCR in Surgut patients with different clinical forms of CAH. NGS was performed on 70 patients with salt-wasting and non-classical clinical forms of 21-hydroxylase deficiency, verified by direct Sanger sequencing and PCR–RFLP analysis. Eleven different pathogenic variants were found in 68.57% (48/70) of patients. Among 92.86% (13/14) of patients with salt-wasting CAH, variants were found to be homozygous, with CYP21A2 gene deletion as the most frequent mutation (46.4% or 13/28 alleles). In the group with non-classical CAH, pathogenic variants were identified only in 60.71% (34/56) of patients. V282L was discovered to be the most common variant in heterozygous carriers (45.45%, 15/33). NGS method identified 2 variants that were not determined by the standard method for major mutations detection: p.C170* and p.W22X, accounting for 3% of all known pathogenic variants. Our data make it possible to clarify the specific spectrum of CYP21A2 gene pathogenic variants in CAH patients from Surgut. The NGS method allows for the identification of rare pathogenic variants (3%) in the CYP21A2 gene that are not included in the conventional PCR–RFLP analysis.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"4 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140128421","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 : 2024-03-07DOI: 10.1186/s43042-024-00501-w
Wessam Sharaf-Eldin
Gene editing can produce irreversible permanent changes to the genetic material at predetermined sequences, avoiding random integration, which is the major drawback of classical gene therapy. The technology has invaded all approaches of genetic engineering and biotechnology with versatile applications in agriculture, industry, and medicine. The present review displays the different approaches and mechanisms of gene editing. Special emphasis has been given to the technology therapeutic applications where all registered clinical trials have been addressed. The Islamic ethical concerns of gene editing have also been highlighted. The great advantages of gene editing technology, coupled with the splendid efforts of scientists to develop systems with superior efficacy and safety would provide an effective avenue for treating a wide range of human diseases in the near future.
{"title":"Technologies of gene editing and related clinical trials for the treatment of genetic and acquired diseases: a systematic review","authors":"Wessam Sharaf-Eldin","doi":"10.1186/s43042-024-00501-w","DOIUrl":"https://doi.org/10.1186/s43042-024-00501-w","url":null,"abstract":"Gene editing can produce irreversible permanent changes to the genetic material at predetermined sequences, avoiding random integration, which is the major drawback of classical gene therapy. The technology has invaded all approaches of genetic engineering and biotechnology with versatile applications in agriculture, industry, and medicine. The present review displays the different approaches and mechanisms of gene editing. Special emphasis has been given to the technology therapeutic applications where all registered clinical trials have been addressed. The Islamic ethical concerns of gene editing have also been highlighted. The great advantages of gene editing technology, coupled with the splendid efforts of scientists to develop systems with superior efficacy and safety would provide an effective avenue for treating a wide range of human diseases in the near future.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"19 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140075050","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 : 2024-03-05DOI: 10.1186/s43042-024-00490-w
Noura Dahbi, Abderrazak El khair, Khadija Cheffi, Lamiaa Habibeddine, Jalal Talbi, Abderraouf Hilali, Hicham El ossmani
Several studies showed that the perpetuation of consanguinity increases homozygosity and homogenizes the population's gene pool. This allows the expression of recessive deleterious mutations and increases the prevalence of genetic disorders and birth defects. Despite the reported negative health effects, consanguinity is still practiced in Morocco. This study aimed to evaluate the prevalence and socio-demographic determinants of consanguinity in the Souss region and to assess the association of this type of union with congenital disabilities and complex diseases. To meet this aim, a survey based on a cross-sectional approach was conducted between January 2019 and January 2020 among 520 randomly selected participants in the Souss region. The findings revealed a high prevalence of consanguinity of 28.46%, with first-cousin unions accounting for 16.15% of all marriages. According to multivariate logistic regression analysis, early age at first marriage, men’s occupation, endogamy, and parental consanguinity were predictive factors for consanguineous unions in the study population. Moreover, the results revealed a significant association between consanguinity and the incidence of physical disabilities (OR = 3.753; [95% CI 1.398–10.074]), mental retardation (OR = 5.219; [95% CI 1.545–17.631]), deafness-mutism (OR = 4.262; [95% CI 1.004–18.089]) and cardiovascular diseases (OR = 2.167; [95% CI 1.036–4.530]). However, no significant association was found between consanguinity and diabetes, cancer, asthma, epilepsy, and psychiatric disorders. Overall, our results suggest a high practice of consanguinity in the Souss population, associated with social, economic, and cultural factors. Consanguineous unions were associated with a high incidence of mental retardation, physical disabilities, deafness-mutism, and cardiovascular diseases. In this population, where marriage between relatives is highly preferred, awareness programs are not sufficient, and genetic studies on consanguinity-related diseases are necessary to provide specific premarital screening and thus increase the efficiency of genetic counseling.
一些研究表明，近亲结婚的延续会增加同源性，并使人口的基因库同质化。这使得隐性有害突变得以表达，增加了遗传疾病和先天缺陷的发病率。尽管有报告称近亲结婚对健康有负面影响，但在摩洛哥仍然存在。本研究旨在评估苏斯地区近亲结婚的普遍程度和社会人口决定因素，并评估这种结合方式与先天残疾和复杂疾病的关联。为实现这一目标，2019 年 1 月至 2020 年 1 月期间，在苏斯地区随机抽取的 520 名参与者中开展了一项基于横断面方法的调查。调查结果显示，近亲结婚率高达 28.46%，嫡亲结合占所有婚姻的 16.15%。根据多变量逻辑回归分析，初婚年龄过早、男性职业、内婚和父母血缘关系是研究人群近亲结婚的预测因素。此外，研究结果表明，近亲结婚与肢体残疾（OR = 3.753; [95% CI 1.398-10.074]）、智力迟钝（OR = 5.219; [95% CI 1.545-17.631]）、聋哑（OR = 4.262; [95% CI 1.004-18.089]）和心血管疾病（OR = 2.167; [95% CI 1.036-4.530]）的发病率有显著关联。然而，近亲结婚与糖尿病、癌症、哮喘、癫痫和精神疾病之间并无明显关联。总之，我们的研究结果表明，在苏斯人中，近亲结婚现象非常普遍，这与社会、经济和文化因素有关。近亲结婚与智力低下、肢体残疾、耳聋-畸形和心血管疾病的高发病率有关。在这一人群中，近亲结婚是非常普遍的现象，因此宣传计划还不够充分，有必要对近亲结婚相关疾病进行遗传学研究，以提供专门的婚前筛查，从而提高遗传咨询的效率。
{"title":"Consanguinity, complex diseases and congenital disabilities in the Souss population (Southern Morocco): a cross-sectional survey","authors":"Noura Dahbi, Abderrazak El khair, Khadija Cheffi, Lamiaa Habibeddine, Jalal Talbi, Abderraouf Hilali, Hicham El ossmani","doi":"10.1186/s43042-024-00490-w","DOIUrl":"https://doi.org/10.1186/s43042-024-00490-w","url":null,"abstract":"Several studies showed that the perpetuation of consanguinity increases homozygosity and homogenizes the population's gene pool. This allows the expression of recessive deleterious mutations and increases the prevalence of genetic disorders and birth defects. Despite the reported negative health effects, consanguinity is still practiced in Morocco. This study aimed to evaluate the prevalence and socio-demographic determinants of consanguinity in the Souss region and to assess the association of this type of union with congenital disabilities and complex diseases. To meet this aim, a survey based on a cross-sectional approach was conducted between January 2019 and January 2020 among 520 randomly selected participants in the Souss region. The findings revealed a high prevalence of consanguinity of 28.46%, with first-cousin unions accounting for 16.15% of all marriages. According to multivariate logistic regression analysis, early age at first marriage, men’s occupation, endogamy, and parental consanguinity were predictive factors for consanguineous unions in the study population. Moreover, the results revealed a significant association between consanguinity and the incidence of physical disabilities (OR = 3.753; [95% CI 1.398–10.074]), mental retardation (OR = 5.219; [95% CI 1.545–17.631]), deafness-mutism (OR = 4.262; [95% CI 1.004–18.089]) and cardiovascular diseases (OR = 2.167; [95% CI 1.036–4.530]). However, no significant association was found between consanguinity and diabetes, cancer, asthma, epilepsy, and psychiatric disorders. Overall, our results suggest a high practice of consanguinity in the Souss population, associated with social, economic, and cultural factors. Consanguineous unions were associated with a high incidence of mental retardation, physical disabilities, deafness-mutism, and cardiovascular diseases. In this population, where marriage between relatives is highly preferred, awareness programs are not sufficient, and genetic studies on consanguinity-related diseases are necessary to provide specific premarital screening and thus increase the efficiency of genetic counseling.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"240 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140036510","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 : 2024-03-05DOI: 10.1186/s43042-024-00500-x
Murat Karaoglan, Gulper Nacarkahya, Emel Hatun Aytac, Mehmet Keskin
Biotinidase deficiency (BTD) is characterized by a wide range of genetic variants. However, the correlation between these variants and the biochemical phenotypes of BTD is not well-established due to the diversity of the BTD gene, the variable nature of biotinidase, and difficulties in measuring enzyme activity. This study aims to identify BTD gene variants in newborns screened for biotinidase deficiency in Southeastern Anatolia and to examine the correlation between these variants and biochemical phenotypes. BTD variant analysis and biotinidase enzyme (BT) activity measurements were performed on 711 newborns. Enzyme activity was measured using the colorimetric method. Biochemical phenotyping was categorized into three groups based on mean residual enzyme activity: profound (≤ 10%), partial (10.1–30%), and normal (> 30.1%). The pathogenicity of BTD gene variants was determined using BTD databases. The biochemical phenotypes were distributed as follows: a) profound: n = 22 (3%), b) partial: n = 95 (13.3%), and c) normal: n = 594 (83.7%). The mean enzyme activities (%) for these groups were 8.79 ± 1.87, 22.67 ± 4.55, and 97.98 ± 17.45, respectively. The most common alleles and their frequencies were p.D444H (n = 526) (37%), p.R157H (n = 172) (12.1%), and p.C33Ffster*36 (n = 73) (9%). The pathogenicity of the variants was as follows: pathogenic: 481 (33.8%), likely pathogenic: 4 (0.2%), and variant of uncertain significance (VUS): 538 (37.8%). In this large cohort in Southeastern Anatolia, the most common alleles were p.D444H, p.R157H, and p.C33Ffster*36 in BTD variants. The results indicate a low concordance between the biochemical phenotype and genotype in newborns with BTD. This study highlights the inadequacy of predicting the biochemical phenotype based solely on variant pathogenicity in biotinidase deficiency during the neonatal period.
{"title":"Genotype-biochemical phenotype analysis in newborns with biotinidase deficiency in Southeastern Anatolia","authors":"Murat Karaoglan, Gulper Nacarkahya, Emel Hatun Aytac, Mehmet Keskin","doi":"10.1186/s43042-024-00500-x","DOIUrl":"https://doi.org/10.1186/s43042-024-00500-x","url":null,"abstract":"Biotinidase deficiency (BTD) is characterized by a wide range of genetic variants. However, the correlation between these variants and the biochemical phenotypes of BTD is not well-established due to the diversity of the BTD gene, the variable nature of biotinidase, and difficulties in measuring enzyme activity. This study aims to identify BTD gene variants in newborns screened for biotinidase deficiency in Southeastern Anatolia and to examine the correlation between these variants and biochemical phenotypes. BTD variant analysis and biotinidase enzyme (BT) activity measurements were performed on 711 newborns. Enzyme activity was measured using the colorimetric method. Biochemical phenotyping was categorized into three groups based on mean residual enzyme activity: profound (≤ 10%), partial (10.1–30%), and normal (> 30.1%). The pathogenicity of BTD gene variants was determined using BTD databases. The biochemical phenotypes were distributed as follows: a) profound: n = 22 (3%), b) partial: n = 95 (13.3%), and c) normal: n = 594 (83.7%). The mean enzyme activities (%) for these groups were 8.79 ± 1.87, 22.67 ± 4.55, and 97.98 ± 17.45, respectively. The most common alleles and their frequencies were p.D444H (n = 526) (37%), p.R157H (n = 172) (12.1%), and p.C33Ffster*36 (n = 73) (9%). The pathogenicity of the variants was as follows: pathogenic: 481 (33.8%), likely pathogenic: 4 (0.2%), and variant of uncertain significance (VUS): 538 (37.8%). In this large cohort in Southeastern Anatolia, the most common alleles were p.D444H, p.R157H, and p.C33Ffster*36 in BTD variants. The results indicate a low concordance between the biochemical phenotype and genotype in newborns with BTD. This study highlights the inadequacy of predicting the biochemical phenotype based solely on variant pathogenicity in biotinidase deficiency during the neonatal period.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"65 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140036682","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}
MicroRNAs have a significant role in the function and development of the hearing system. Idiopathic sudden sensorineural hearing loss (SSNHL) is a complicated disorder with no long-established reason. Since microRNAs play imperative roles in every aspect of the neural system, their dysregulation may contribute to the onset of SSNHL. The current study aimed to assess the expression patterns of microRNA processing elements (DROSHA, DICER, and DGCR-8) as the vital factors in microRNA biology that can affect the expression levels of microRNA. This study assessed DROSHA, DICER, and DGCR-8 mRNA expression levels in the peripheral blood mononuclear cells (PBMC) of 50 patients with SSNHL and 50 matched controls. After the isolation of PBMC, total RNA was extracted, and the expression levels of DROSHA, DICER, and DGCR-8 genes were evaluated using quantitative real-time PCR. The results illustrated significant up-regulation of DICER and DGCR-8 genes in SSNHL patients at the mRNA level. Furthermore, despite no significant change in DROSHA level, DICER and DGCR-8 were significantly correlated with SSNHL. However, there was no significant correlation between these gene expressions and the clinicopathological features of patients. This study verified for the first time that the DGCR_8 and DICER mRNA expression levels were significantly up-regulated in patients with SSNHL, proposing that microRNAs and their processing pathways play key roles in the progression and development of SSNHL.
{"title":"Evaluation of expression levels of microRNA processing elements in patients with sudden sensorineural hearing loss","authors":"Yalda Jabbari-Moghaddam, Dariush Shanehbandi, Milad Asadi, Saiedeh Razi-Soofiyani, Vahideh Hateftabar","doi":"10.1186/s43042-024-00496-4","DOIUrl":"https://doi.org/10.1186/s43042-024-00496-4","url":null,"abstract":"MicroRNAs have a significant role in the function and development of the hearing system. Idiopathic sudden sensorineural hearing loss (SSNHL) is a complicated disorder with no long-established reason. Since microRNAs play imperative roles in every aspect of the neural system, their dysregulation may contribute to the onset of SSNHL. The current study aimed to assess the expression patterns of microRNA processing elements (DROSHA, DICER, and DGCR-8) as the vital factors in microRNA biology that can affect the expression levels of microRNA. This study assessed DROSHA, DICER, and DGCR-8 mRNA expression levels in the peripheral blood mononuclear cells (PBMC) of 50 patients with SSNHL and 50 matched controls. After the isolation of PBMC, total RNA was extracted, and the expression levels of DROSHA, DICER, and DGCR-8 genes were evaluated using quantitative real-time PCR. The results illustrated significant up-regulation of DICER and DGCR-8 genes in SSNHL patients at the mRNA level. Furthermore, despite no significant change in DROSHA level, DICER and DGCR-8 were significantly correlated with SSNHL. However, there was no significant correlation between these gene expressions and the clinicopathological features of patients. This study verified for the first time that the DGCR_8 and DICER mRNA expression levels were significantly up-regulated in patients with SSNHL, proposing that microRNAs and their processing pathways play key roles in the progression and development of SSNHL.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"88 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140046765","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 : 2024-02-29DOI: 10.1186/s43042-024-00498-2
Ale Eba, Syed Tasleem Raza, Irshad A. Wani, Zeba Siddiqi, Mohammad Abbas, Sanchita Srivastava, Farzana Mahdi
Coronary artery disease (CAD) is a complex medical condition characterized by atherosclerotic plaque accumulation in coronary arteries, leading to narrowed blood vessels and impaired blood flow. Endothelial dysfunction, smooth muscle cell proliferation, and various risk factors contribute to CAD development. Matricellular proteins, including thrombospondins (THBS), play crucial roles in vascular processes and cardiac function. A case–control study was conducted among 296 participants from Era's Lucknow Medical College and Hospital, India, to investigate genetic variations in THBS1 (N700S) and THBS2 (3′ UTR T → G) in relation to CAD. Genomic DNA was isolated, and PCR–RFLP was employed for genotyping. Clinical and biochemical parameters were assessed, and statistical analyses were performed using SPSS software. The study revealed that age, serum cholesterol, HDL, VLDL, and LDL were significantly associated with CAD in the Indian population. However, no statistically significant associations were found between triglyceride and serum creatinine levels, as well as the studied THBS1 and THBS2 genetic polymorphisms, and CAD. The analysis of genotypic and allelic frequencies did not indicate significant associations with CAD risk. This study suggests that specific genetic variations in THBS1 and THBS2 may not be strongly linked to the development or risk of CAD in the studied Indian population. The associations observed between age, lipid profiles, and CAD highlight the multifactorial nature of CAD susceptibility. Further research with larger sample sizes and diverse populations is warranted to validate these findings and explore additional genetic factors contributing to CAD in specific populations.
{"title":"cxsAssociation study between single nucleotide polymorphism in thrombospondins THBS1 gene and THBS2 gene and coronary artery disease in Indian population","authors":"Ale Eba, Syed Tasleem Raza, Irshad A. Wani, Zeba Siddiqi, Mohammad Abbas, Sanchita Srivastava, Farzana Mahdi","doi":"10.1186/s43042-024-00498-2","DOIUrl":"https://doi.org/10.1186/s43042-024-00498-2","url":null,"abstract":"Coronary artery disease (CAD) is a complex medical condition characterized by atherosclerotic plaque accumulation in coronary arteries, leading to narrowed blood vessels and impaired blood flow. Endothelial dysfunction, smooth muscle cell proliferation, and various risk factors contribute to CAD development. Matricellular proteins, including thrombospondins (THBS), play crucial roles in vascular processes and cardiac function. A case–control study was conducted among 296 participants from Era's Lucknow Medical College and Hospital, India, to investigate genetic variations in THBS1 (N700S) and THBS2 (3′ UTR T → G) in relation to CAD. Genomic DNA was isolated, and PCR–RFLP was employed for genotyping. Clinical and biochemical parameters were assessed, and statistical analyses were performed using SPSS software. The study revealed that age, serum cholesterol, HDL, VLDL, and LDL were significantly associated with CAD in the Indian population. However, no statistically significant associations were found between triglyceride and serum creatinine levels, as well as the studied THBS1 and THBS2 genetic polymorphisms, and CAD. The analysis of genotypic and allelic frequencies did not indicate significant associations with CAD risk. This study suggests that specific genetic variations in THBS1 and THBS2 may not be strongly linked to the development or risk of CAD in the studied Indian population. The associations observed between age, lipid profiles, and CAD highlight the multifactorial nature of CAD susceptibility. Further research with larger sample sizes and diverse populations is warranted to validate these findings and explore additional genetic factors contributing to CAD in specific populations.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"10 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140008368","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 : 2024-02-28DOI: 10.1186/s43042-024-00497-3
Rosa Catapano, Filippo Russo, Marco Rosetti, Giovanni Poletti, Silvia Trombetti, Raffaele Sessa, Tommaso Fasano, Sauro Maoggi, Sante Roperto, Michela Grosso
<p><b>Dear Editor,</b></p><p>Acquired alpha-thalassemia mental retardation X-linked (ATRX) mutations are associated with the onset of α-thalassemia in several hematological malignancies including myelodysplasia, acute lymphoblastic leukemia, myelofibrosis, essential thrombocythemia, and acute myeloid leukemia (acquired α-thalassemia myelodisplastic syndrome, ATMDS) [1]. The ATRX gene (NM_000489.6) is located at Xq21.1 and encodes a chromatin remodeling protein which contributes to regulate the structure and function of chromatin in centromeric heterochromatin and telomeric domains to control different cellular pathways including DNA damage response and senescence mechanisms [2, 3]. ATRX is also involved in the epigenetic regulation of α-globin genes: loss-of-function mutations in the ATRX gene cause the transcriptional repression of the α-globin gene (HBA), thus resulting in a decreasing production of α-globin chains [4]. In this regard, mutations of the ATRX gene have been reported in association with a rare inherited pathology called X-linked α-thalassemia and mental retardation syndrome (or ATR-X syndrome) characterized by mental retardation, facial and urogenital abnormalities along with an α-thalassemia trait with elevated levels of β-globin or γ-globin tetramers (HbH or Barts' hemoglobin), the amount of which is directly related to the severity of the α-globin chain deficiency [5].</p><p>Here we report a novel single-nucleotide variant (SNV) in the <i>ATRX</i> gene, found by Next-Generation Sequencing (NGS) analysis in a 77-year-old Italian man previously healthy who had been hospitalized for myelofibrosis and was referred to our Centre to investigate the possible genetic cause of an acquired form of α-thalassemia with elevated levels of HbH. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Naples Federico II (project approval number 443/21). Genomic DNA was extracted using the Nucleon BACC3 kit (GE Healthcare, Life Sciences, Chicago, IL, USA) and analyzed by a customized NGS gene panel recently developed by our group to identify acquired or inherited mutations associated with thalassemic disorders. The DNA libraries were prepared with the SureSelect<sup>XT HS</sup> Target Enrichment System kit (Agilent Technologies, Santa Clara, CA, USA) after enzymatic fragmentation and according to the manufacturer’s protocol. Library quality and quantity were checked with the TapeStation system (Agilent Technologies) and Qubit dsDNA High Sensitivity assay kit on Qubit Fluorometer (Thermo Fisher Scientific, Waltham, MA, USA), respectively. Libraries were sequenced with MiSeq Reagent Kit v2 (300-cycles) by loading a concentrated pool (9 pM) and 1% Phix on a MiSeq Illumina® instrument (Illumina; San Diego, CA, USA). To exclude any kind of contamination, a blank negative control was included, and it followed all procedure’s steps, from DNA extraction to sequencing. Data analysis
{"title":"Identification of a novel ATR-X mutation causative of acquired α-thalassemia in a myelofibrosis patient","authors":"Rosa Catapano, Filippo Russo, Marco Rosetti, Giovanni Poletti, Silvia Trombetti, Raffaele Sessa, Tommaso Fasano, Sauro Maoggi, Sante Roperto, Michela Grosso","doi":"10.1186/s43042-024-00497-3","DOIUrl":"https://doi.org/10.1186/s43042-024-00497-3","url":null,"abstract":"<p><b>Dear Editor,</b></p><p>Acquired alpha-thalassemia mental retardation X-linked (ATRX) mutations are associated with the onset of α-thalassemia in several hematological malignancies including myelodysplasia, acute lymphoblastic leukemia, myelofibrosis, essential thrombocythemia, and acute myeloid leukemia (acquired α-thalassemia myelodisplastic syndrome, ATMDS) [1]. The ATRX gene (NM_000489.6) is located at Xq21.1 and encodes a chromatin remodeling protein which contributes to regulate the structure and function of chromatin in centromeric heterochromatin and telomeric domains to control different cellular pathways including DNA damage response and senescence mechanisms [2, 3]. ATRX is also involved in the epigenetic regulation of α-globin genes: loss-of-function mutations in the ATRX gene cause the transcriptional repression of the α-globin gene (HBA), thus resulting in a decreasing production of α-globin chains [4]. In this regard, mutations of the ATRX gene have been reported in association with a rare inherited pathology called X-linked α-thalassemia and mental retardation syndrome (or ATR-X syndrome) characterized by mental retardation, facial and urogenital abnormalities along with an α-thalassemia trait with elevated levels of β-globin or γ-globin tetramers (HbH or Barts' hemoglobin), the amount of which is directly related to the severity of the α-globin chain deficiency [5].</p><p>Here we report a novel single-nucleotide variant (SNV) in the <i>ATRX</i> gene, found by Next-Generation Sequencing (NGS) analysis in a 77-year-old Italian man previously healthy who had been hospitalized for myelofibrosis and was referred to our Centre to investigate the possible genetic cause of an acquired form of α-thalassemia with elevated levels of HbH. The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Naples Federico II (project approval number 443/21). Genomic DNA was extracted using the Nucleon BACC3 kit (GE Healthcare, Life Sciences, Chicago, IL, USA) and analyzed by a customized NGS gene panel recently developed by our group to identify acquired or inherited mutations associated with thalassemic disorders. The DNA libraries were prepared with the SureSelect<sup>XT HS</sup> Target Enrichment System kit (Agilent Technologies, Santa Clara, CA, USA) after enzymatic fragmentation and according to the manufacturer’s protocol. Library quality and quantity were checked with the TapeStation system (Agilent Technologies) and Qubit dsDNA High Sensitivity assay kit on Qubit Fluorometer (Thermo Fisher Scientific, Waltham, MA, USA), respectively. Libraries were sequenced with MiSeq Reagent Kit v2 (300-cycles) by loading a concentrated pool (9 pM) and 1% Phix on a MiSeq Illumina® instrument (Illumina; San Diego, CA, USA). To exclude any kind of contamination, a blank negative control was included, and it followed all procedure’s steps, from DNA extraction to sequencing. Data analysis","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"4 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140008449","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}
Despite substantial advancements in gastric cancer treatment in recent years, our understanding of the disease’s pathophysiology and progression processes remains limited, and the prognosis for gastric cancer patients remains poor. This study investigated potential prognostic indicators based on m7G-associated long non-coding RNA (lncRNA) and its relationship with gastric cancer (STAD). The researchers used RNA-seq and prognostic data from TCGA, employing Cox regression, co-expression network analysis, and multivariate Cox regression to identify relevant lncRNAs. We compiled four m7G-related lncRNAs into a single signature. We found it may be used as a prognostic indicator for gastric cancer. The m7G-related lncRNA profile had an area under the curve of 0.710, significantly more diagnostic than clinicopathological markers. The study also found that the TMB and tumor microenvironment were associated with gastric cancer risk, highlighting their signature’s potential utility for personalized treatment and disease monitoring. This study provides a novel signature of m7G-related lncRNAs that can be used as a prognostic indicator for gastric cancer and may help guide the development of targeted immunotherapy for the condition.
{"title":"A novel N7-methylguanosine-associated feature predicts prognosis in gastric cancer","authors":"Shixing Zhao, Wenbo Zhao, Chunxia Yao, Yunxiao Tian","doi":"10.1186/s43042-024-00495-5","DOIUrl":"https://doi.org/10.1186/s43042-024-00495-5","url":null,"abstract":"Despite substantial advancements in gastric cancer treatment in recent years, our understanding of the disease’s pathophysiology and progression processes remains limited, and the prognosis for gastric cancer patients remains poor. This study investigated potential prognostic indicators based on m7G-associated long non-coding RNA (lncRNA) and its relationship with gastric cancer (STAD). The researchers used RNA-seq and prognostic data from TCGA, employing Cox regression, co-expression network analysis, and multivariate Cox regression to identify relevant lncRNAs. We compiled four m7G-related lncRNAs into a single signature. We found it may be used as a prognostic indicator for gastric cancer. The m7G-related lncRNA profile had an area under the curve of 0.710, significantly more diagnostic than clinicopathological markers. The study also found that the TMB and tumor microenvironment were associated with gastric cancer risk, highlighting their signature’s potential utility for personalized treatment and disease monitoring. This study provides a novel signature of m7G-related lncRNAs that can be used as a prognostic indicator for gastric cancer and may help guide the development of targeted immunotherapy for the condition.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139978775","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 : 2024-02-25DOI: 10.1186/s43042-024-00491-9
Anam Farooqui, Naaila Tamkeen, Safia Tazyeen, Sher Ali, Romana Ishrat
Turner syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. The information on the genotype–phenotype relationship in TS is inadequate. Comparing the healthy and Turner syndrome patients may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC). The coexpression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Two of them, SMCHD1 and PGK1, have already been reported to be involved in TS. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1, were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified four clusters in the PPI network constructed from the top 15 KME enriched in significant functions. Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human healthcare system.
{"title":"System biology approach to delineate expressional difference in the blood mononuclear cells between healthy and Turner syndrome individuals","authors":"Anam Farooqui, Naaila Tamkeen, Safia Tazyeen, Sher Ali, Romana Ishrat","doi":"10.1186/s43042-024-00491-9","DOIUrl":"https://doi.org/10.1186/s43042-024-00491-9","url":null,"abstract":"Turner syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. The information on the genotype–phenotype relationship in TS is inadequate. Comparing the healthy and Turner syndrome patients may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC). The coexpression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Two of them, SMCHD1 and PGK1, have already been reported to be involved in TS. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1, were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified four clusters in the PPI network constructed from the top 15 KME enriched in significant functions. Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human healthcare system.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"59 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139969083","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 : 2024-02-14DOI: 10.1186/s43042-024-00484-8
Farhana Siddiqi Mitu, Md. Murad Hossain, Shuvo Chandra Das, Md. Mafizul Islam, Dhirendra Nath Barman, Shipan Das Gupta
Type 2 diabetes mellitus (T2DM) is considered to be a polygenic disorder that emerges as a result of complicated gene-environment interactions. Several investigations revealed that SLC30A8 rs13266634 polymorphism elevates T2DM risk. T2DM and hypertension (HTN) are often found to be coexist. Compared to normotensive non-diabetic controls, T2DM patients with HTN have a fourfold increased risk of cardiovascular disease (CVD). The average age of T2DM diagnosis is decreasing, and ‘early onset of T2DM’ in adolescents and young adults is an emerging worldwide health concern. The objective of this study was to examine the potential correlations of SLC30A8 rs13266634 polymorphism with T2DM and T2DM-related CVD and HTN as well as ‘early onset of T2DM’ in the Noakhali region. This case–control study involved 163 T2DM patients and 75 healthy controls for analysis of SLC30A8-rs13266634 polymorphism. Genotyping of this polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. MedCalc and Gene Calc programs were used for statistical analysis. A statistically significant association of SLC30A8 rs13266634 (P < 0.05) with T2DM was found in dominant, over dominant and allele models. But this study found no evidence of a connection between SLC30A8-rs13266634 with CVD, HTN, or ‘early onset of T2DM’ in any models. Furthermore, T2DM patients had higher total cholesterol (TC) and triglyceride (TG) levels than non-diabetics individuals. This study revealed a substantial association between the variation in SLC30A8-rs13266634 and the increased risk of developing T2DM within a sample of the Noakhali population in Bangladesh. However, no significant associations were observed between SLC30A8-rs13266634 and T2DM-related cardiovascular disease (CVD), hypertension (HTN), or the early onset of T2DM within this specific population.
{"title":"Association of SLC30A8 rs13266634 gene polymorphism with type 2 diabetes mellitus (T2DM) in a population of Noakhali, Bangladesh: a case–control study","authors":"Farhana Siddiqi Mitu, Md. Murad Hossain, Shuvo Chandra Das, Md. Mafizul Islam, Dhirendra Nath Barman, Shipan Das Gupta","doi":"10.1186/s43042-024-00484-8","DOIUrl":"https://doi.org/10.1186/s43042-024-00484-8","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) is considered to be a polygenic disorder that emerges as a result of complicated gene-environment interactions. Several investigations revealed that SLC30A8 rs13266634 polymorphism elevates T2DM risk. T2DM and hypertension (HTN) are often found to be coexist. Compared to normotensive non-diabetic controls, T2DM patients with HTN have a fourfold increased risk of cardiovascular disease (CVD). The average age of T2DM diagnosis is decreasing, and ‘early onset of T2DM’ in adolescents and young adults is an emerging worldwide health concern. The objective of this study was to examine the potential correlations of SLC30A8 rs13266634 polymorphism with T2DM and T2DM-related CVD and HTN as well as ‘early onset of T2DM’ in the Noakhali region. This case–control study involved 163 T2DM patients and 75 healthy controls for analysis of SLC30A8-rs13266634 polymorphism. Genotyping of this polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. MedCalc and Gene Calc programs were used for statistical analysis. A statistically significant association of SLC30A8 rs13266634 (P < 0.05) with T2DM was found in dominant, over dominant and allele models. But this study found no evidence of a connection between SLC30A8-rs13266634 with CVD, HTN, or ‘early onset of T2DM’ in any models. Furthermore, T2DM patients had higher total cholesterol (TC) and triglyceride (TG) levels than non-diabetics individuals. This study revealed a substantial association between the variation in SLC30A8-rs13266634 and the increased risk of developing T2DM within a sample of the Noakhali population in Bangladesh. However, no significant associations were observed between SLC30A8-rs13266634 and T2DM-related cardiovascular disease (CVD), hypertension (HTN), or the early onset of T2DM within this specific population.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"7 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139770057","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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