Pub Date : 2024-03-20DOI: 10.1186/s43042-024-00506-5
Antonio Alejandro Esperón Álvarez, Inés Virginia Noa Hechavarría, Ixchel López Reyes, Teresa Collazo Mesa
Von Hippel-Lindau (VHL) syndrome is an autosomal dominantly inherited disorder that predisposes to multiple neoplasms. Patients may develop hemangioblastomas of the central nervous system and retina, multiple cysts in the pancreas and kidneys, renal carcinoma, and pheochromocytomas, among other lesions. This disease is caused by germline genetic variants in the VHL gene. The regulation of the alpha subunit of hypoxia-inducible factor-1 is the key tumor suppressor function of the VHL protein. To date, more than seven hundred variants have been reported in VHL gene. This study aimed to investigate the molecular etiology of VHL syndrome in Cuban patients. DNA samples from twenty-two individuals were analyzed by Sanger sequencing or enzymatic restriction. The analysis identified four novel pathogenic variants for the Cuban population: c.463 + 2T > C, C162W, R167W, and S183X, in addition to D121G and R161X, previously described in another work. The diagnosis was confirmed in seven patients with clinical manifestations and family history. Two at-risk family members without clinical signs were positive for presymptomatic diagnosis. The spectrum of germinal point mutations of VHL gene in Cuban patients was updated. The presence of genetic variants was ruled out in eight asymptomatic relatives, which is a psychological relief for these individuals. The results allow for offering other at-risk relatives the presymptomatic diagnosis and the possibility of receiving genetic counseling.
{"title":"Germline variants in the Von Hippel-Lindau tumor suppressor gene in Cuban patients","authors":"Antonio Alejandro Esperón Álvarez, Inés Virginia Noa Hechavarría, Ixchel López Reyes, Teresa Collazo Mesa","doi":"10.1186/s43042-024-00506-5","DOIUrl":"https://doi.org/10.1186/s43042-024-00506-5","url":null,"abstract":"Von Hippel-Lindau (VHL) syndrome is an autosomal dominantly inherited disorder that predisposes to multiple neoplasms. Patients may develop hemangioblastomas of the central nervous system and retina, multiple cysts in the pancreas and kidneys, renal carcinoma, and pheochromocytomas, among other lesions. This disease is caused by germline genetic variants in the VHL gene. The regulation of the alpha subunit of hypoxia-inducible factor-1 is the key tumor suppressor function of the VHL protein. To date, more than seven hundred variants have been reported in VHL gene. This study aimed to investigate the molecular etiology of VHL syndrome in Cuban patients. DNA samples from twenty-two individuals were analyzed by Sanger sequencing or enzymatic restriction. The analysis identified four novel pathogenic variants for the Cuban population: c.463 + 2T > C, C162W, R167W, and S183X, in addition to D121G and R161X, previously described in another work. The diagnosis was confirmed in seven patients with clinical manifestations and family history. Two at-risk family members without clinical signs were positive for presymptomatic diagnosis. The spectrum of germinal point mutations of VHL gene in Cuban patients was updated. The presence of genetic variants was ruled out in eight asymptomatic relatives, which is a psychological relief for these individuals. The results allow for offering other at-risk relatives the presymptomatic diagnosis and the possibility of receiving genetic counseling.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140166452","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 : 2024-03-14DOI: 10.1186/s43042-024-00507-4
Gloria Garavito De Egea, Alex Domínguez-Vargas, Luis Fang, Nicole Pereira-Sanandrés, Jonathan Rodríguez, Gustavo Aroca-Martinez, Zilac Espítatela, Clara Malagón, Antonio Iglesias-Gamarra, Ana Moreno-Woo, Guillermo López-Lluch, Eduardo Egea
Adiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN. Ninety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for MTHFR rs1801131 and FGG rs2066865 SNPs. Compared to healthy controls, pLN patients exhibited significantly greater serum leptin (11.3 vs. 18.2 ng/mL, p < 0.001) and adiponectin (18.2 vs. 2.7 ug/mL, p < 0.001). Adiponectin levels were positively correlated with proteinuria (p < 0.05), while leptin levels positively correlated with proteinuria, SLE disease activity index-2000 (SLEDAI-2K), and cyclophosphamide usage (all p < 0.05). There was no significant association between MTHFR rs1801131 or FGG rs2066865 SNPs and pLN in either codominant or allelic models (all p > 0.05). However, the AG genotype of FGG gene rs2066865 SNP was significantly associated with high leptin levels (> 15 ng/mL) (p = 0.01). Serum adiponectin and leptin levels are associated with pathological manifestations of pLN. High leptin levels are associated with the AG genotype of FGG rs2066865 SNP in pLN patients, suggesting direct involvement in disease progression and potential utility as a disease biomarker.
脂联素和瘦素是调节新陈代谢的关键因素。小儿狼疮肾炎（pLN）是影响肾脏的儿童系统性红斑狼疮（SLE）的一种表现形式，与脂肪因子水平受损有关，这表明脂肪因子在小儿狼疮肾炎的发病机制中发挥作用。本研究旨在探讨特定单核苷酸多态性（SNPs）--亚甲基四氢叶酸还原酶（MTHFR）rs1801131和纤维蛋白原γ链（FGG）rs2066865--与pLN患者血清中瘦素和脂肪连素水平之间的潜在关系。研究共纳入了 98 名 pLN 患者和 100 名对照组。采用酶联免疫吸附法测定血清瘦素和脂肪连素水平。对 MTHFR rs1801131 和 FGG rs2066865 SNPs 进行了 DNA 提取和实时 PCR 基因分型。与健康对照组相比，pLN 患者的血清瘦素明显增加（11.3 vs. 18.2 ng/mL，P 0.05）。然而，FGG 基因 rs2066865 SNP 的 AG 基因型与高瘦素水平（> 15 ng/mL）明显相关（p = 0.01）。血清脂肪连接蛋白和瘦素水平与 pLN 的病理表现相关。高瘦素水平与pLN患者FGG rs2066865 SNP的AG基因型相关，这表明瘦素直接参与了疾病的进展，并有可能成为一种疾病生物标志物。
{"title":"Exploring the interplay of MTHFR and FGG polymorphisms with serum levels of adiponectin and leptin in pediatric lupus nephritis: a pilot study","authors":"Gloria Garavito De Egea, Alex Domínguez-Vargas, Luis Fang, Nicole Pereira-Sanandrés, Jonathan Rodríguez, Gustavo Aroca-Martinez, Zilac Espítatela, Clara Malagón, Antonio Iglesias-Gamarra, Ana Moreno-Woo, Guillermo López-Lluch, Eduardo Egea","doi":"10.1186/s43042-024-00507-4","DOIUrl":"https://doi.org/10.1186/s43042-024-00507-4","url":null,"abstract":"Adiponectin and leptin are pivotal in the regulation of metabolism. Pediatric lupus nephritis (pLN), a manifestation of childhood systemic lupus erythematosus (SLE) affecting the kidneys, is associated with impaired adipokine levels, suggesting a role in pLN pathogenesis. The aim of this study was to explore the potential relationship between specific single-nucleotide polymorphisms (SNPs)—methylenetetrahydrofolate reductase (MTHFR) rs1801131 and fibrinogen gamma chain (FGG) rs2066865—and the serum levels of leptin and adiponectin in patients with pLN. Ninety-eight pLN patients and one hundred controls were enrolled in the study. Serum leptin and adiponectin levels were measured using ELISA. DNA extraction and real-time PCR genotyping were performed for MTHFR rs1801131 and FGG rs2066865 SNPs. Compared to healthy controls, pLN patients exhibited significantly greater serum leptin (11.3 vs. 18.2 ng/mL, p < 0.001) and adiponectin (18.2 vs. 2.7 ug/mL, p < 0.001). Adiponectin levels were positively correlated with proteinuria (p < 0.05), while leptin levels positively correlated with proteinuria, SLE disease activity index-2000 (SLEDAI-2K), and cyclophosphamide usage (all p < 0.05). There was no significant association between MTHFR rs1801131 or FGG rs2066865 SNPs and pLN in either codominant or allelic models (all p > 0.05). However, the AG genotype of FGG gene rs2066865 SNP was significantly associated with high leptin levels (> 15 ng/mL) (p = 0.01). Serum adiponectin and leptin levels are associated with pathological manifestations of pLN. High leptin levels are associated with the AG genotype of FGG rs2066865 SNP in pLN patients, suggesting direct involvement in disease progression and potential utility as a disease biomarker.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140153887","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 : 2024-03-13DOI: 10.1186/s43042-024-00505-6
Mutiat A. Abdulkareem, Bunmi A. Owolabi, Emmanuel S. Saheed, Remilekun F. Aromolaran, Rukayat M. Bashiru, Toheeb A. Jumah, Doris U. Chijioke, Onyinyechi J. Amaechi, Fehintoluwa C. Adeleke, Omiyale O. Charles, Tunde S. Oluokun
This review article gives an insight into the genetic factors and the role of pancreatic amylase in type 2 diabetes (T2D). Diabetes is a non-communicable, multifactorial, heritable, complex, and irreversible disease of public health burden with a global prevalence rate of 6.28%, about 6% in sub-Saharan Africa, and 1.7% in Nigeria. T2D is recognized as the ninth leading cause of mortality worldwide. This disease is yet to be diagnosed in a significant number of people who live with it in underdeveloped and developing countries like Nigeria due to the lack of free or subsidized access to health care, especially medical checkups, inadequate health facilities, government policies, and negligence. Consequently, undiagnosed cases of T2D have contributed to the prevalence of this disease and its comorbidities -hypertension and chronic kidney disease. Obesity, age, race and ethnicity, inactivity, family history, underlying illness, and unhealthy diets are prominent undisputable predisposing factors of T2D. Pancreatic amylase is a type of amylase produced in the pancreas, known to hydrolyze starch and prone to mutations, but most of the genetic components, causative polymorphisms, and affected genes are yet unknown. Even as insulin secretion is found to be influenced by the loci, the causation of T2D cannot be inferred. Pancreatic amylase was observed to be the most relevant digestive enzyme, whose role is to bind to glycoprotein N-glycan to activate starch digestion. In a malfunctioning pancreas, little or no insulin is generated to keep the blood glucose at an appropriate level, thereby resulting in T2D.
{"title":"Genetic factors and the role of pancreatic amylase in the pathogenesis of type 2 diabetes","authors":"Mutiat A. Abdulkareem, Bunmi A. Owolabi, Emmanuel S. Saheed, Remilekun F. Aromolaran, Rukayat M. Bashiru, Toheeb A. Jumah, Doris U. Chijioke, Onyinyechi J. Amaechi, Fehintoluwa C. Adeleke, Omiyale O. Charles, Tunde S. Oluokun","doi":"10.1186/s43042-024-00505-6","DOIUrl":"https://doi.org/10.1186/s43042-024-00505-6","url":null,"abstract":"This review article gives an insight into the genetic factors and the role of pancreatic amylase in type 2 diabetes (T2D). Diabetes is a non-communicable, multifactorial, heritable, complex, and irreversible disease of public health burden with a global prevalence rate of 6.28%, about 6% in sub-Saharan Africa, and 1.7% in Nigeria. T2D is recognized as the ninth leading cause of mortality worldwide. This disease is yet to be diagnosed in a significant number of people who live with it in underdeveloped and developing countries like Nigeria due to the lack of free or subsidized access to health care, especially medical checkups, inadequate health facilities, government policies, and negligence. Consequently, undiagnosed cases of T2D have contributed to the prevalence of this disease and its comorbidities -hypertension and chronic kidney disease. Obesity, age, race and ethnicity, inactivity, family history, underlying illness, and unhealthy diets are prominent undisputable predisposing factors of T2D. Pancreatic amylase is a type of amylase produced in the pancreas, known to hydrolyze starch and prone to mutations, but most of the genetic components, causative polymorphisms, and affected genes are yet unknown. Even as insulin secretion is found to be influenced by the loci, the causation of T2D cannot be inferred. Pancreatic amylase was observed to be the most relevant digestive enzyme, whose role is to bind to glycoprotein N-glycan to activate starch digestion. In a malfunctioning pancreas, little or no insulin is generated to keep the blood glucose at an appropriate level, thereby resulting in T2D.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140129668","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 : 2024-03-12DOI: 10.1186/s43042-024-00504-7
Khyber Saify, Mostafa Saadat
Methadone has been reported to downregulate the expression of glutathione S-transferase P1 (GSTP1) among nine antioxidant genes in SH-SY5Y cells after both short- and long-term treatment. GSTP1 plays a key role in the detoxification of many xenobiotics and is frequently associated with various diseases, especially tumors. The objective of this study is to determine whether this change is reversible. Two different treatment protocols were used. The first protocol evaluated the reversibility of the GSTP1 mRNA change, while the second protocol evaluated the methylation status of the GSTP1 promoter site. To investigate the reversibility of the GSTP1 mRNA change, SH-SY5Y cells were treated with methadone. The drug was then removed from the medium and the cells were cultured in methadone-free medium for a period of time. GSTP1 mRNA levels were expressed as cycle threshold (Ct) values using TATA box-binding protein as a calibrator gene. Methylation at the promoter site was detected by bisulfite treatment. The analysis of variance revealed no significant change in GSTP1 mRNA levels in the cells after methadone was removed from the medium of methadone-treated cells. The study also examined the methylation status of a CpG island in the promoter of GSTP1 in the treated cells. The results demonstrate that although methadone downregulates the mRNA level of GSTP1 in treated cells, it does not induce methylation in the GSTP1 promoter region. The expression of the GSTP1 remains downregulated even after methadone removal from SH-SY5Y cell culture medium; however, methylation of the GSTP1 promoter site does not play a role in this process.
{"title":"Irreversible methadone-induced GSTP1 downregulation in SH-SY5Y cells","authors":"Khyber Saify, Mostafa Saadat","doi":"10.1186/s43042-024-00504-7","DOIUrl":"https://doi.org/10.1186/s43042-024-00504-7","url":null,"abstract":"Methadone has been reported to downregulate the expression of glutathione S-transferase P1 (GSTP1) among nine antioxidant genes in SH-SY5Y cells after both short- and long-term treatment. GSTP1 plays a key role in the detoxification of many xenobiotics and is frequently associated with various diseases, especially tumors. The objective of this study is to determine whether this change is reversible. Two different treatment protocols were used. The first protocol evaluated the reversibility of the GSTP1 mRNA change, while the second protocol evaluated the methylation status of the GSTP1 promoter site. To investigate the reversibility of the GSTP1 mRNA change, SH-SY5Y cells were treated with methadone. The drug was then removed from the medium and the cells were cultured in methadone-free medium for a period of time. GSTP1 mRNA levels were expressed as cycle threshold (Ct) values using TATA box-binding protein as a calibrator gene. Methylation at the promoter site was detected by bisulfite treatment. The analysis of variance revealed no significant change in GSTP1 mRNA levels in the cells after methadone was removed from the medium of methadone-treated cells. The study also examined the methylation status of a CpG island in the promoter of GSTP1 in the treated cells. The results demonstrate that although methadone downregulates the mRNA level of GSTP1 in treated cells, it does not induce methylation in the GSTP1 promoter region. The expression of the GSTP1 remains downregulated even after methadone removal from SH-SY5Y cell culture medium; however, methylation of the GSTP1 promoter site does not play a role in this process.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140128454","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 : 2024-03-12DOI: 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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
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