Pub Date : 2024-02-12DOI: 10.1186/s43042-024-00494-6
Hala T. El-Bassyouni, Engy A. Ashaat, Khaled Hamed, Maha Rashed, Azza E. Abd-Elnaby, Marwa Shehab
The hallmarks of Emanuel syndrome are pre- and postnatal growth retardation, microcephaly, global developmental delay, ear anomalies, and in males, heart, kidney, and genital abnormalities. This study describes the atypical features of Emanuel syndrome, a rare chromosomal disorder. The patient had several physical features that are common in Emanuel syndrome, such as microcephaly, hypotonia, and ear anomalies. However, he exhibited certain unusual characteristics, including the lack of a prominent forehead, epicanthic folds, and a downward slanting palpebral fissure. There was infratentorial brain involution with a minor infarction in the left cerebral hemisphere and cerebellar hypoplasia on the magnetic resonance imaging (MRI) scan of the brain. Additionally, the patient had bilateral mild hearing loss and an aberrant epileptogenic pattern on the electroencephalogram (EEG). Orodental examination showed a long philtrum, everted fissured thick lower lip, highly attached labial frenum, and prominent median palatine raphe. The karyotype revealed 45XY t(11;22)(p15.5;q11.22), which is different from the typical karyotype of Emanuel syndrome. This case sheds light on the possibility of alternative genetic mechanisms, beyond chromosomal abnormalities, in patients presenting with multiple congenital anomalies and facial dysmorphism.
{"title":"Emanuel syndrome due to unusual pattern","authors":"Hala T. El-Bassyouni, Engy A. Ashaat, Khaled Hamed, Maha Rashed, Azza E. Abd-Elnaby, Marwa Shehab","doi":"10.1186/s43042-024-00494-6","DOIUrl":"https://doi.org/10.1186/s43042-024-00494-6","url":null,"abstract":"The hallmarks of Emanuel syndrome are pre- and postnatal growth retardation, microcephaly, global developmental delay, ear anomalies, and in males, heart, kidney, and genital abnormalities. This study describes the atypical features of Emanuel syndrome, a rare chromosomal disorder. The patient had several physical features that are common in Emanuel syndrome, such as microcephaly, hypotonia, and ear anomalies. However, he exhibited certain unusual characteristics, including the lack of a prominent forehead, epicanthic folds, and a downward slanting palpebral fissure. There was infratentorial brain involution with a minor infarction in the left cerebral hemisphere and cerebellar hypoplasia on the magnetic resonance imaging (MRI) scan of the brain. Additionally, the patient had bilateral mild hearing loss and an aberrant epileptogenic pattern on the electroencephalogram (EEG). Orodental examination showed a long philtrum, everted fissured thick lower lip, highly attached labial frenum, and prominent median palatine raphe. The karyotype revealed 45XY t(11;22)(p15.5;q11.22), which is different from the typical karyotype of Emanuel syndrome. This case sheds light on the possibility of alternative genetic mechanisms, beyond chromosomal abnormalities, in patients presenting with multiple congenital anomalies and facial dysmorphism.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"6 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769818","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}
Anterior segment dysgenesis (ASD) disorders comprises of spectrum of developmental conditions affecting the structures of angle of anterior chamber including cornea, iris, and lens. These conditions are characterized by both autosomal dominant and recessive patterns of inheritance often with incomplete penetrance/variable expressivity. A significant overlap among phenotypes attributed to mutations in different ASD genes is well recognized. We present a case involving a 29-year-old pregnant woman referred for genetic screening and counseling. She had a 7-year-old male child with congenital bilateral corneal opacity, and his elder sister also exhibited similar findings. Exome sequencing identified a novel variant in the CYP1B1 gene in a homozygous state, which was associated with anterior segment dysgenesis. Both parents were found to be carriers of the same variant, while the sister had the same variant in a homozygous state. Genotype–phenotype correlation was performed, and it was concluded that the novel variant could be responsible for the eye changes in both siblings. The parents sought prenatal diagnosis for the current pregnancy, which was deemed possible. This case underscores the importance of genetic testing in such rare diseases, as it can assist in early diagnosis, management, and prognosis. It also aids clinicians and parents in making decisions regarding the continuation of the pregnancy at the appropriate time.
{"title":"Novel mutation as a cause of anterior segment dysgenesis leading to blindness in progeny: the genetics decoded!","authors":"Kumari Pritti, Vineet Mishra, Somesh Aggarwal, Mehul Mistri, Manisha Chhetry","doi":"10.1186/s43042-024-00493-7","DOIUrl":"https://doi.org/10.1186/s43042-024-00493-7","url":null,"abstract":"Anterior segment dysgenesis (ASD) disorders comprises of spectrum of developmental conditions affecting the structures of angle of anterior chamber including cornea, iris, and lens. These conditions are characterized by both autosomal dominant and recessive patterns of inheritance often with incomplete penetrance/variable expressivity. A significant overlap among phenotypes attributed to mutations in different ASD genes is well recognized. We present a case involving a 29-year-old pregnant woman referred for genetic screening and counseling. She had a 7-year-old male child with congenital bilateral corneal opacity, and his elder sister also exhibited similar findings. Exome sequencing identified a novel variant in the CYP1B1 gene in a homozygous state, which was associated with anterior segment dysgenesis. Both parents were found to be carriers of the same variant, while the sister had the same variant in a homozygous state. Genotype–phenotype correlation was performed, and it was concluded that the novel variant could be responsible for the eye changes in both siblings. The parents sought prenatal diagnosis for the current pregnancy, which was deemed possible. This case underscores the importance of genetic testing in such rare diseases, as it can assist in early diagnosis, management, and prognosis. It also aids clinicians and parents in making decisions regarding the continuation of the pregnancy at the appropriate time.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"308 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769910","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 : 2024-02-09DOI: 10.1186/s43042-024-00489-3
Safa Meshaal, Rabab El Hawary, Dalia Abd Elaziz, Alia Eldash, Rania Darwish, Aya Erfan, Sohilla Lotfy, Mai M. Saad, Engy Chohayeb, Radwa Alkady, Jeannette Boutros, Nermeen Galal, Aisha Elmarsafy
Caspase recruitment domain family, member 11 (CARD11) is an important protein which plays a fundamental role in the activation of NF-κβ pathway in lymphocytes. CARD11 deficiency can be inherited in either autosomal dominant or autosomal recessive forms and present with different phenotypes including combined immunodeficiency, atopic dermatitis, and other variable manifestations. The present report describes clinical phenotypes and immunological defects of two unrelated patients with missense homozygous variants in CARD11 presenting with combined immunodeficiency (CID) and atopic skin disease resembling that reported in dominant negative CARD11 deficiency. The patients underwent next generation sequencing, immunophenotyping of T and B subsets by flow cytometry, T cell stimulation, and evaluation of CARD11 expression. Both patients had features suggesting CID including repeated pneumoniae with ICU admissions, chronic diarrhea, and itchy atopic skin disease. Patient-1 has homozygous missense variant in the C terminal domain (c.2839G > A, p.Glu947Lys), and patient-2 has homozygous variant in the inhibitory domain (c.1073C > G, p.Pro568Arg). Both have profound defects in Tregs with normal recent thymic emigrants, memory, and naïve CD4+ T cells. However, in response to stimulation, T cells failed to upregulate the expression of CD25. CARD11 expression by flow cytometry was decreased rather than abolished as previously described in patients with autosomal recessive CARD11 deficiency. B cells showed marked deficiency of switched memory and increase in transitional B cells. Missense variants causing CARD11 deficiency may affect the protein function rather than the expression and can result in a phenotype combining the atopic skin disease and the features of CID.
Caspase 募集结构域家族成员 11（CARD11）是一种重要的蛋白质，在淋巴细胞激活 NF-κβ 通路的过程中发挥着重要作用。CARD11 缺乏症可为常染色体显性遗传或常染色体隐性遗传，并表现出不同的表型，包括联合免疫缺陷、特应性皮炎和其他可变表现。本报告描述了两名无亲属关系的 CARD11 错义同源变异患者的临床表型和免疫缺陷，他们表现为联合免疫缺陷症（CID）和特应性皮肤病，类似于已报道的显性阴性 CARD11 缺乏症。患者接受了新一代测序、流式细胞术对 T 和 B 亚群进行免疫分型、T 细胞刺激和 CARD11 表达评估。这两名患者都有提示 CID 的特征，包括反复肺炎并住进 ICU、慢性腹泻和瘙痒性特异性皮肤病。患者-1 的 C 端结构域存在同源错义变异（c.2839G > A，p.Glu947Lys），患者-2 的抑制结构域存在同源变异（c.1073C > G，p.Pro568Arg）。二者的Tregs均存在严重缺陷，近期胸腺移入者、记忆和幼稚CD4+T细胞均正常。然而，在刺激下，T 细胞不能上调 CD25 的表达。通过流式细胞术检测，CARD11的表达减少了，而不是像以前在常染色体隐性CARD11缺乏症患者中描述的那样消失了。B 细胞表现出明显的切换记忆缺陷，过渡性 B 细胞增多。导致 CARD11 缺乏症的错义变体可能会影响蛋白质的功能而不是表达，并可能导致结合特应性皮肤病和 CID 特征的表型。
{"title":"Novel homozygous CARD11 variants in two patients with combined immunodeficiency and atopic skin disease","authors":"Safa Meshaal, Rabab El Hawary, Dalia Abd Elaziz, Alia Eldash, Rania Darwish, Aya Erfan, Sohilla Lotfy, Mai M. Saad, Engy Chohayeb, Radwa Alkady, Jeannette Boutros, Nermeen Galal, Aisha Elmarsafy","doi":"10.1186/s43042-024-00489-3","DOIUrl":"https://doi.org/10.1186/s43042-024-00489-3","url":null,"abstract":"Caspase recruitment domain family, member 11 (CARD11) is an important protein which plays a fundamental role in the activation of NF-κβ pathway in lymphocytes. CARD11 deficiency can be inherited in either autosomal dominant or autosomal recessive forms and present with different phenotypes including combined immunodeficiency, atopic dermatitis, and other variable manifestations. The present report describes clinical phenotypes and immunological defects of two unrelated patients with missense homozygous variants in CARD11 presenting with combined immunodeficiency (CID) and atopic skin disease resembling that reported in dominant negative CARD11 deficiency. The patients underwent next generation sequencing, immunophenotyping of T and B subsets by flow cytometry, T cell stimulation, and evaluation of CARD11 expression. Both patients had features suggesting CID including repeated pneumoniae with ICU admissions, chronic diarrhea, and itchy atopic skin disease. Patient-1 has homozygous missense variant in the C terminal domain (c.2839G > A, p.Glu947Lys), and patient-2 has homozygous variant in the inhibitory domain (c.1073C > G, p.Pro568Arg). Both have profound defects in Tregs with normal recent thymic emigrants, memory, and naïve CD4+ T cells. However, in response to stimulation, T cells failed to upregulate the expression of CD25. CARD11 expression by flow cytometry was decreased rather than abolished as previously described in patients with autosomal recessive CARD11 deficiency. B cells showed marked deficiency of switched memory and increase in transitional B cells. Missense variants causing CARD11 deficiency may affect the protein function rather than the expression and can result in a phenotype combining the atopic skin disease and the features of CID.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"11 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769903","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}
Breast cancer (BC) is the most common female cancers in many countries including Syria. Familial breast cancer or previous family cancer history are considered significant risk factors. Therefore, detecting the prevalence and founder mutations in the population facilitates genetic counselling, risk assessment and the development of a cost-effective screening strategy. In this study, we investigated the three germ-line founder mutations in the BRCA1/2 genes: [NM_007294.4 (BRCA1):c.68_69del (p.Glu23fs), NM_007294.4 (BRCA1):c.5266dup (p.Gln1756fs) and NM_000059.4 (BRCA2):c.5946del (p.Ser1982fs)], to examine their incidence and frequency in early-onset breast cancer cases and determine if they are connected to familial breast cancer. One hundred early diagnosed BC females (≤ 40 years old) with no other type of cancer were recruited. Genomic DNA was isolated from peripheral blood samples, and mutations were investigated using the Amplification-Created Restriction Site (ACRS) method. The family history of cancer was observed in 61% of the cases, of which 35% were breast cancer; however, none of the screened mutations were detected among BC patients. The investigated germ-line mutations were not common among Syrian female patients with early-onset BC and were not associated with familial BC. Other mutations in the BRCA1/2 genes or other genes may have a contributing role. Future studies and the need to launch nationwide mutation screening tests for BRCA 1/BRCA2 in the Syrian population are recommended.
{"title":"BRCA mutations: screening for germ-line founder mutations among early-onset Syrian breast cancer patients","authors":"Salma Wahabi Alzahabi, Maher Saifo, Ghalia Abou Alchamat","doi":"10.1186/s43042-024-00492-8","DOIUrl":"https://doi.org/10.1186/s43042-024-00492-8","url":null,"abstract":"Breast cancer (BC) is the most common female cancers in many countries including Syria. Familial breast cancer or previous family cancer history are considered significant risk factors. Therefore, detecting the prevalence and founder mutations in the population facilitates genetic counselling, risk assessment and the development of a cost-effective screening strategy. In this study, we investigated the three germ-line founder mutations in the BRCA1/2 genes: [NM_007294.4 (BRCA1):c.68_69del (p.Glu23fs), NM_007294.4 (BRCA1):c.5266dup (p.Gln1756fs) and NM_000059.4 (BRCA2):c.5946del (p.Ser1982fs)], to examine their incidence and frequency in early-onset breast cancer cases and determine if they are connected to familial breast cancer. One hundred early diagnosed BC females (≤ 40 years old) with no other type of cancer were recruited. Genomic DNA was isolated from peripheral blood samples, and mutations were investigated using the Amplification-Created Restriction Site (ACRS) method. The family history of cancer was observed in 61% of the cases, of which 35% were breast cancer; however, none of the screened mutations were detected among BC patients. The investigated germ-line mutations were not common among Syrian female patients with early-onset BC and were not associated with familial BC. Other mutations in the BRCA1/2 genes or other genes may have a contributing role. Future studies and the need to launch nationwide mutation screening tests for BRCA 1/BRCA2 in the Syrian population are recommended.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"7 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769820","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 : 2024-02-06DOI: 10.1186/s43042-024-00476-8
Vandit Sevak, Rathika Chinniah, Sasiharan Pandi, K. Sampathkumar, T. Dinakaran, Balakrishnan Karuppiah
The present study was undertaken to examine the role of IL-4 (− 590 C/T) (rs2243250) and IL-6 (− 174G/C) (rs1800795) polymorphism and the serum levels of IL-4 and IL-6 in chronic kidney disease (CKD). The IL-4 (− 590C/T) and IL-6 (− 174 G/C) polymorphisms were genotyped in 132 CKD patients and 161 controls using PCR–RFLP. Serum IL-4 and IL-6 quantifications were performed by ELISA. Significant susceptible associations of CT genotype (OR = 4.56; p < 1.84 × 10–9) and T allele (OR = 1.56; p < 0.010) of IL-4 (− 590C/T) and CC genotype (OR = 2.63; p < 0.032) of IL-6 (− 174G/C) were observed for CKD. The CC genotype (OR = 0.27; p < 9.314 × 10–7) and C allele (OR = 0.63; p < 0.010) of IL-4 (− 590 C/T) revealed strong protective associations. Five-fold increased levels were observed for both IL-6 (p < 0.0001) and IL-4 (p < 0.0043) cytokines in CKD patients than the controls. The IL-4 serum levels (pg/ml) increased significantly in patients with CT and TT genotypes of IL-4 (− 590 C/T) than the controls (6.18 ± 1.80 vs. 3.33 ± 0.48 and 6.14 ± 1.96 vs. 3.21 ± 0.56 respectively). For IL-6 (− 174 G/C) polymorphism, the patients with CC genotype (6.50 ± 1.30 vs. 3.49 ± 1.39) revealed with higher IL-6 serum levels followed by GC genotype (5.00 ± 1.91 vs. 4.01 ± 1.74). The genotypes of IL-4 (590 C/T) and IL-6 (174 G/C) polymorphisms contribute differential susceptibility in south Indian CKD patients. A fivefold increased serum levels of IL-4 (anti-inflammatory) and IL-6 (pro- and anti-inflammatory) cytokines were documented in CKD patients. There observed an opposite trend in disease association for these two cytokines and associated SNPs with CKD in south India.
{"title":"Association of IL-4 (− 590 C/T) and IL-6 (− 174 G/C) gene polymorphism in South Indian CKD patients","authors":"Vandit Sevak, Rathika Chinniah, Sasiharan Pandi, K. Sampathkumar, T. Dinakaran, Balakrishnan Karuppiah","doi":"10.1186/s43042-024-00476-8","DOIUrl":"https://doi.org/10.1186/s43042-024-00476-8","url":null,"abstract":"The present study was undertaken to examine the role of IL-4 (− 590 C/T) (rs2243250) and IL-6 (− 174G/C) (rs1800795) polymorphism and the serum levels of IL-4 and IL-6 in chronic kidney disease (CKD). The IL-4 (− 590C/T) and IL-6 (− 174 G/C) polymorphisms were genotyped in 132 CKD patients and 161 controls using PCR–RFLP. Serum IL-4 and IL-6 quantifications were performed by ELISA. Significant susceptible associations of CT genotype (OR = 4.56; p < 1.84 × 10–9) and T allele (OR = 1.56; p < 0.010) of IL-4 (− 590C/T) and CC genotype (OR = 2.63; p < 0.032) of IL-6 (− 174G/C) were observed for CKD. The CC genotype (OR = 0.27; p < 9.314 × 10–7) and C allele (OR = 0.63; p < 0.010) of IL-4 (− 590 C/T) revealed strong protective associations. Five-fold increased levels were observed for both IL-6 (p < 0.0001) and IL-4 (p < 0.0043) cytokines in CKD patients than the controls. The IL-4 serum levels (pg/ml) increased significantly in patients with CT and TT genotypes of IL-4 (− 590 C/T) than the controls (6.18 ± 1.80 vs. 3.33 ± 0.48 and 6.14 ± 1.96 vs. 3.21 ± 0.56 respectively). For IL-6 (− 174 G/C) polymorphism, the patients with CC genotype (6.50 ± 1.30 vs. 3.49 ± 1.39) revealed with higher IL-6 serum levels followed by GC genotype (5.00 ± 1.91 vs. 4.01 ± 1.74). The genotypes of IL-4 (590 C/T) and IL-6 (174 G/C) polymorphisms contribute differential susceptibility in south Indian CKD patients. A fivefold increased serum levels of IL-4 (anti-inflammatory) and IL-6 (pro- and anti-inflammatory) cytokines were documented in CKD patients. There observed an opposite trend in disease association for these two cytokines and associated SNPs with CKD in south India.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"12 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139769900","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 : 2024-02-03DOI: 10.1186/s43042-024-00480-y
Tamer H. A. Ammar, Ghada M. M. Al-Ettribi, Maha M. A. Abo Hashish, Tarek M. Farid, Amany A. Abou-Elalla, Manal M. Thomas
Isolated growth hormone deficiency (IGHD) is a hereditary disorder that causes significant short stature. GHD has a reported incidence of 1/4000–1/10,000 births. It is caused by mutations in the major somatotroph axis genes, involving GH1, codes for growth hormone, GHSR, and GHRHR, codes for growth hormone secretagogue receptor and growth hormone-releasing hormone receptor, respectively. The present study aims to examine the clinical phenotype and investigate the genetic etiology of ten Egyptian patients with type I isolated growth hormone insufficiency. Patients recruited for the study were clinically diagnosed by two provocation tests and were subjected to a thorough history, clinical examination, and anthropometric measurements. Sanger sequencing and mutational analysis of the three genes, GH1, GHSR, and GHRHR, was our approach, performed in all enrolled IGHD patients. The variants identified were analyzed using the biological, population, sequence variants, and clinical genetics databases. Prediction of the pathogenicity of the novel variants was done by in silico prediction tools following the American College of Medical Genetics and Genomics (ACMG) guidelines. Sanger sequencing revealed a previously reported pathogenic mutation (NM_000823.4: c.1069C > T; p.Arg357Cys) in the GHRHR gene in one patient and a novel frameshift variant (NM_198407.2: c.1043dup; Ser349Leu fs*6) in the GHSR gene in another patient. This is the fourth report highlighting the autosomal dominant inheritance of the GHSR mutation as a cause of isolated growth hormone deficiency. A number of previously reported variants, but of rare frequency, were identified in this study. In our IGHD cases, 90% of the patients were underweight, 50% had anemia, and 80% showed hypovitaminosis D. Our findings broaden the mutational spectrum underlying the IGHD in Egyptian patients and point out the importance of mutation screening of the GHSR and GHRHR genes. This study also acknowledges the autosomal dominant mode of inheritance of the GHSR mutation as a cause for dwarfism.
{"title":"Screening of GHSR, GHRHR, GH1 genes in isolated growth hormone deficiency disease in Egyptian patients","authors":"Tamer H. A. Ammar, Ghada M. M. Al-Ettribi, Maha M. A. Abo Hashish, Tarek M. Farid, Amany A. Abou-Elalla, Manal M. Thomas","doi":"10.1186/s43042-024-00480-y","DOIUrl":"https://doi.org/10.1186/s43042-024-00480-y","url":null,"abstract":"Isolated growth hormone deficiency (IGHD) is a hereditary disorder that causes significant short stature. GHD has a reported incidence of 1/4000–1/10,000 births. It is caused by mutations in the major somatotroph axis genes, involving GH1, codes for growth hormone, GHSR, and GHRHR, codes for growth hormone secretagogue receptor and growth hormone-releasing hormone receptor, respectively. The present study aims to examine the clinical phenotype and investigate the genetic etiology of ten Egyptian patients with type I isolated growth hormone insufficiency. Patients recruited for the study were clinically diagnosed by two provocation tests and were subjected to a thorough history, clinical examination, and anthropometric measurements. Sanger sequencing and mutational analysis of the three genes, GH1, GHSR, and GHRHR, was our approach, performed in all enrolled IGHD patients. The variants identified were analyzed using the biological, population, sequence variants, and clinical genetics databases. Prediction of the pathogenicity of the novel variants was done by in silico prediction tools following the American College of Medical Genetics and Genomics (ACMG) guidelines. Sanger sequencing revealed a previously reported pathogenic mutation (NM_000823.4: c.1069C > T; p.Arg357Cys) in the GHRHR gene in one patient and a novel frameshift variant (NM_198407.2: c.1043dup; Ser349Leu fs*6) in the GHSR gene in another patient. This is the fourth report highlighting the autosomal dominant inheritance of the GHSR mutation as a cause of isolated growth hormone deficiency. A number of previously reported variants, but of rare frequency, were identified in this study. In our IGHD cases, 90% of the patients were underweight, 50% had anemia, and 80% showed hypovitaminosis D. Our findings broaden the mutational spectrum underlying the IGHD in Egyptian patients and point out the importance of mutation screening of the GHSR and GHRHR genes. This study also acknowledges the autosomal dominant mode of inheritance of the GHSR mutation as a cause for dwarfism.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"23 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139665670","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}
<p>Following publication of the original article [1], the authors informed us that the author Maysam Mard-Soltani is Co-first Author of this paper.</p><p>The original article has been corrected.</p><ol data-track-component="outbound reference"><li data-counter="1."><p>Ehsani S et al (2023) Egypt J Med Hum Genet 24:84. https://doi.org/10.1186/s43042-023-00464-4</p><p>Article Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><span>Author notes</span><ol><li><p>Maysam Mard-Soltani is Co-first Author of this paper</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran</p><p>Samira Ehsani & Gholamreza Shahsavari</p></li><li><p>Department of Clinical Biochemistry, School of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran</p><p>Maysam Mard-Soltani</p></li><li><p>Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran</p><p>Fatemeh Ahmadpour</p></li><li><p>Department of Clinical Biochemistry, Lorestan University of Medical Sciences, Khorramabad, Iran</p><p>Samira Ehsani & Gholamreza Shahsavari</p></li></ol><span>Authors</span><ol><li><span>Samira Ehsani</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Maysam Mard-Soltani</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Fatemeh Ahmadpour</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Gholamreza Shahsavari</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Corresponding author</h3><p>Correspondence to Gholamreza Shahsavari.</p><h3>Publisher's Note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permis
原文[1]发表后，作者通知我们，作者 Maysam Mard-Soltani 是本文的共同第一作者。原文已更正。Ehsani S et al (2023) Egypt J Med Hum Genet 24:84. https://doi.org/10.1186/s43042-023-00464-4Article Google Scholar Download referencesAuthor notesMaysam Mard-Soltani is Co-first Author of this paperAuthors and AffiliationsCardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, IranSamira Ehsani &；Gholamreza ShahsavariDepartment of Clinical Biochemistry, School of Medical Sciences, Dezful University of Medical Sciences, Dezful, IranMaysam Mard-SoltaniNutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, IranFatemeh AhmadpourDepartment of Clinical Biochemistry, Lorestan University of Medical Sciences, Khorramabad, IranSamira Ehsani &；Gholamreza Shahsavari作者Samira Ehsani查看作者发表的文章您也可以在PubMed Google Scholar中搜索该作者Maysam Mard-SoltaniView 作者发表的作品您也可以在 PubMed Google ScholarFatemeh AhmadpourView 作者发表的作品您也可以在 PubMed Google ScholarGholamreza ShahsavariView 作者发表的作品您也可以在 PubMed Google ScholarCorresponding author给 Gholamreza Shahsavari 的回信。开放获取本文采用知识共享署名 4.0 国际许可协议进行许可，该协议允许以任何媒介或格式使用、共享、改编、分发和复制，只要您适当注明原作者和来源，提供知识共享许可协议的链接，并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出许可使用范围，您需要直接从版权所有者处获得许可。要查看该许可的副本，请访问 http://creativecommons.org/licenses/by/4.0/.Reprints and permissionsCite this articleEhsani, S., Mard-Soltani, M., Ahmadpour, F. et al. Correction：动脉粥样硬化患者血液单核细胞中 miR-138-5p、miR-132-3p、SIRT1、STAT3 和 CD36 与致动脉粥样硬化指数的关系。Egypt J Med Hum Genet 25, 15 (2024). https://doi.org/10.1186/s43042-024-00473-xDownload citationPublished: 31 January 2024DOI: https://doi.org/10.1186/s43042-024-00473-xShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative.
{"title":"Correction: Association between miR-138-5p, miR-132-3p, SIRT1, STAT3, and CD36 and atherogenic indices in blood mononuclear cells from patients with atherosclerosis","authors":"Samira Ehsani, Maysam Mard-Soltani, Fatemeh Ahmadpour, Gholamreza Shahsavari","doi":"10.1186/s43042-024-00473-x","DOIUrl":"https://doi.org/10.1186/s43042-024-00473-x","url":null,"abstract":"<p>Following publication of the original article [1], the authors informed us that the author Maysam Mard-Soltani is Co-first Author of this paper.</p><p>The original article has been corrected.</p><ol data-track-component=\"outbound reference\"><li data-counter=\"1.\"><p>Ehsani S et al (2023) Egypt J Med Hum Genet 24:84. https://doi.org/10.1186/s43042-023-00464-4</p><p>Article Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><span>Author notes</span><ol><li><p>Maysam Mard-Soltani is Co-first Author of this paper</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran</p><p>Samira Ehsani & Gholamreza Shahsavari</p></li><li><p>Department of Clinical Biochemistry, School of Medical Sciences, Dezful University of Medical Sciences, Dezful, Iran</p><p>Maysam Mard-Soltani</p></li><li><p>Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran</p><p>Fatemeh Ahmadpour</p></li><li><p>Department of Clinical Biochemistry, Lorestan University of Medical Sciences, Khorramabad, Iran</p><p>Samira Ehsani & Gholamreza Shahsavari</p></li></ol><span>Authors</span><ol><li><span>Samira Ehsani</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Maysam Mard-Soltani</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Fatemeh Ahmadpour</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Gholamreza Shahsavari</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Corresponding author</h3><p>Correspondence to Gholamreza Shahsavari.</p><h3>Publisher's Note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permis","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"11 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139648380","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 : 2024-01-30DOI: 10.1186/s43042-024-00477-7
Noha M. El-Shishtawy, Fatma M. El Marzouky, Hanan A. El-Hagrasy
Cellular and molecular changes occur during aging, decreasing organ function. The aging process was measured by several biomarkers, including DNA methylation (DNAm), an epigenetic change regulating gene expression, which is highly accurate at predicting biological age. DNAm is heritable and therefore varies between different populations. To assess blood DNA methylation changes as epigenetic clocks in the male and female Egyptian population. Pyrosequencing was used to measure the methylation of nine CpG sites in blood samples from 100 healthy Egyptians (18–69 years) using a cross-sectional study. Two age predicted models based on the ELOVL2 gene were compared in three age categories and correlated in all age groups despite decreasing accuracy with increasing age. The mean absolute deviation (MAD) using the 1st and 2nd age predicted models for 18–40 years was 1.06 and 2.7, respectively; for 41–60 years, it was 4.4 and 3.8, respectively; and for > 60 years, it was 7.7 and 7.0, respectively. No significant differences in DNA methylation were found between the sexes. DNA methylation of the ELOVL2 gene can be used as an accurate biomarker for age estimation. Additionally, this method has the potential to be more accurate than traditional methods of age estimation.
衰老过程中会发生细胞和分子变化，降低器官功能。衰老过程是通过几种生物标志物来测量的，其中包括 DNA 甲基化（DNAm），这是一种调节基因表达的表观遗传变化，在预测生物年龄方面具有很高的准确性。DNAm 具有遗传性，因此在不同人群之间存在差异。目的是评估作为表观遗传时钟的埃及男性和女性人群的血液 DNA 甲基化变化。通过一项横断面研究，对 100 名健康埃及人（18-69 岁）的血液样本中 9 个 CpG 位点的甲基化情况进行了热释光测序测量。在三个年龄组中比较了两种基于 ELOVL2 基因的年龄预测模型，尽管准确性随着年龄的增加而降低，但它们在所有年龄组中都具有相关性。使用第一和第二年龄预测模型得出的平均绝对偏差（MAD），18-40 岁分别为 1.06 和 2.7；41-60 岁分别为 4.4 和 3.8；大于 60 岁分别为 7.7 和 7.0。男女之间的 DNA 甲基化没有明显差异。ELOVL2 基因的 DNA 甲基化可作为准确估算年龄的生物标志物。此外，这种方法有可能比传统的年龄估计方法更准确。
{"title":"DNA methylation of ELOVL2 gene as an epigenetic marker of age among Egyptian population","authors":"Noha M. El-Shishtawy, Fatma M. El Marzouky, Hanan A. El-Hagrasy","doi":"10.1186/s43042-024-00477-7","DOIUrl":"https://doi.org/10.1186/s43042-024-00477-7","url":null,"abstract":"Cellular and molecular changes occur during aging, decreasing organ function. The aging process was measured by several biomarkers, including DNA methylation (DNAm), an epigenetic change regulating gene expression, which is highly accurate at predicting biological age. DNAm is heritable and therefore varies between different populations. To assess blood DNA methylation changes as epigenetic clocks in the male and female Egyptian population. Pyrosequencing was used to measure the methylation of nine CpG sites in blood samples from 100 healthy Egyptians (18–69 years) using a cross-sectional study. Two age predicted models based on the ELOVL2 gene were compared in three age categories and correlated in all age groups despite decreasing accuracy with increasing age. The mean absolute deviation (MAD) using the 1st and 2nd age predicted models for 18–40 years was 1.06 and 2.7, respectively; for 41–60 years, it was 4.4 and 3.8, respectively; and for > 60 years, it was 7.7 and 7.0, respectively. No significant differences in DNA methylation were found between the sexes. DNA methylation of the ELOVL2 gene can be used as an accurate biomarker for age estimation. Additionally, this method has the potential to be more accurate than traditional methods of age estimation.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"156 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139649415","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}
According to the increasing trend of COPD, the timely diagnosis and treatment of the disease can reduce the high costs to the health systems. Therefore, by biological calculation methods, signaling pathways and genes involved in this disease can be obtained and used to design drugs and other treatment methods. By using biological calculations, we determined that curcumin can affect this disease and its genes and signaling pathways. Our goal in this study was to find the genes by which curcumin exerts its effect and can maintain the function of corticosteroids against oxidizing agents. By finding the genes, it is possible to find precisely the pathways by which curcumin works, which can be used to design other drugs that cause these pathways and minimize their side effects. This study considers healthy samples (with/without curcumin) and oxygen-free radicals (with/without curcumin). Finally, statistical algorithms extract meaningful genes as effective biomarkers to investigate curcumin's effects and signaling pathways in COPD. The results show that the genes finally obtained as the most critical genes confirmed by the literature are effective in COPD. Finally, curcumin was input in SwissTargetPrediction to identify potential protein receptors. We used LigPlot+ software to visualize the receptor–ligand binding result provided by iGEMDOCK. The data showed that the most significant genes in each group have been confirmed in other studies to be effective in this disease, and protein–protein interaction networks can be established between them to investigate their roles.
{"title":"Evaluation of the effects of curcumin on chronic obstructive pulmonary disease with a bio-computational approach","authors":"Mohammad Maboudian, Elham Amjad, Solmaz Asnaashari, Siavoush Dastmalchi, Babak Sokouti, Yousef Javadzadeh","doi":"10.1186/s43042-024-00486-6","DOIUrl":"https://doi.org/10.1186/s43042-024-00486-6","url":null,"abstract":"According to the increasing trend of COPD, the timely diagnosis and treatment of the disease can reduce the high costs to the health systems. Therefore, by biological calculation methods, signaling pathways and genes involved in this disease can be obtained and used to design drugs and other treatment methods. By using biological calculations, we determined that curcumin can affect this disease and its genes and signaling pathways. Our goal in this study was to find the genes by which curcumin exerts its effect and can maintain the function of corticosteroids against oxidizing agents. By finding the genes, it is possible to find precisely the pathways by which curcumin works, which can be used to design other drugs that cause these pathways and minimize their side effects. This study considers healthy samples (with/without curcumin) and oxygen-free radicals (with/without curcumin). Finally, statistical algorithms extract meaningful genes as effective biomarkers to investigate curcumin's effects and signaling pathways in COPD. The results show that the genes finally obtained as the most critical genes confirmed by the literature are effective in COPD. Finally, curcumin was input in SwissTargetPrediction to identify potential protein receptors. We used LigPlot+ software to visualize the receptor–ligand binding result provided by iGEMDOCK. The data showed that the most significant genes in each group have been confirmed in other studies to be effective in this disease, and protein–protein interaction networks can be established between them to investigate their roles.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"24 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139578474","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}
Apoptosis, also known as the programmed death of cells, is responsible for maintaining the homeostasis of tissues, and this function is carried out by caspases. The process of apoptosis is carried out via two distinct pathways: the extrinsic pathway, which is governed by death receptors, and the intrinsic pathway, also known as the mitochondrial pathway. The BCL-2 protein family encoded by the BCL-2 gene, located at the 18q21.33 chromosomal location, is in charge of regulating the intrinsic pathway, which is responsible for inducing cell death via the permeabilization of the mitochondrial membrane and the release of apoptosis-inducing components. The BCL-2 homology (BH1, BH2, BH3, BH4) domains of this family proteins are crucial for their functioning, and their common BH domains allow interactions between members of the same family and can also serve as indications of pro- or anti-apoptotic activity. A direct correlation may be shown between the overexpression of BCL-2 and the postponement of cell death. It has been determined that a change in the expression of BCL-2 is the root cause of a variety of malignancies, including lung, breast, melanoma, and chronic lymphocytic leukemia, multiple sclerosis, diabetes. In this review, we addressed the genetic information and structural homology of BCL-2 family members. Further, we elucidate the pro-apoptotic and anti-apoptotic roles of the family members. This review highlights the most recent developments in the BCL-2 protein family and presents evidence that targeting this family proteins may have a positive impact on the treatment of medical problems that are still underserved.
{"title":"Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context","authors":"Md. Saddam, Shamrat Kumar Paul, Mohammad Ahsan Habib, Md. Abrar Fahim, Afsana Mimi, Saiful Islam, Bristi Paul, Md Mostofa Uddin Helal","doi":"10.1186/s43042-024-00485-7","DOIUrl":"https://doi.org/10.1186/s43042-024-00485-7","url":null,"abstract":"Apoptosis, also known as the programmed death of cells, is responsible for maintaining the homeostasis of tissues, and this function is carried out by caspases. The process of apoptosis is carried out via two distinct pathways: the extrinsic pathway, which is governed by death receptors, and the intrinsic pathway, also known as the mitochondrial pathway. The BCL-2 protein family encoded by the BCL-2 gene, located at the 18q21.33 chromosomal location, is in charge of regulating the intrinsic pathway, which is responsible for inducing cell death via the permeabilization of the mitochondrial membrane and the release of apoptosis-inducing components. The BCL-2 homology (BH1, BH2, BH3, BH4) domains of this family proteins are crucial for their functioning, and their common BH domains allow interactions between members of the same family and can also serve as indications of pro- or anti-apoptotic activity. A direct correlation may be shown between the overexpression of BCL-2 and the postponement of cell death. It has been determined that a change in the expression of BCL-2 is the root cause of a variety of malignancies, including lung, breast, melanoma, and chronic lymphocytic leukemia, multiple sclerosis, diabetes. In this review, we addressed the genetic information and structural homology of BCL-2 family members. Further, we elucidate the pro-apoptotic and anti-apoptotic roles of the family members. This review highlights the most recent developments in the BCL-2 protein family and presents evidence that targeting this family proteins may have a positive impact on the treatment of medical problems that are still underserved.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139578532","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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