Balkan Journal of Medical Genetics最新文献_第9页

Implication of VDR Rs7975232 and FCGR2A Rs1801274 Gene Polymorphisms in the Risk and the Prognosis of autoimmune Thyroid Diseases in the Tunisian Population. VDR Rs7975232和FCGR2A Rs1801274基因多态性在突尼斯人群自身免疫性甲状腺疾病风险和预后中的意义

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0011

S Mestiri, I Zaaber, I Nasr, H Marmouch

{"title":"Implication of VDR Rs7975232 and FCGR2A Rs1801274 Gene Polymorphisms in the Risk and the Prognosis of autoimmune Thyroid Diseases in the Tunisian Population.","authors":"S Mestiri, I Zaaber, I Nasr, H Marmouch","doi":"10.2478/bjmg-2020-0011","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0011","url":null,"abstract":"Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) that cause hypothyroidism and hyperthyroidism, respectively. The vitamin D receptor (VDR) and the Fey receptor IIA (FcγRIIA), are implicated in the etiology of AITD. This study was conducted to examine the implication of VDR rs7975232 and FCGR2A rs 1801274 variations in the susceptibility and the prognosis of AITD in the Tunisian population. The rs7975232 and rs1801274 (R131H) polymorphisms were analyzed in 162 controls and 162 AITD patients (106 HT and 56 GD) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification of refractory mutation system-PCR (ARMS-PCR), respectively. No significant difference was demonstrated for the rs7975232 between patients and controls. However, a significant association was shown between the rs1801274 polymorphism and AITD or HT in the dominant (p = 0.03 or p = 0.01), codominant (p = 0.019 or p = 0.026) and allelic (p = 0.011 or p = 0.012) models. The rs7975232 was associated with the absence or the presence of anti-thyroglobulin antibody, with the age of AITD and GD patients during the first diagnosis (p = 0.01 and p = 0.009, respectively) and with a high T4 level at the beginning of HT disease. However, the FCGR2A gene polymorphism was associated with a low T4 level at the beginning of GD disease. In conclusion, this study indicates that only the FCGR2A variation could be related to AITD and HT susceptibility and that VDR and FCGR2A gene variations constitute factors to prognosticate the severity of AITD, HT and GD.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/c3/bjmg-23-069.PMC7474221.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

A New Splice-site Mutation of SPINK5 Gene in the Netherton Syndrome with Different Clinical Features: A Case Report. 不同临床特征的内瑟顿综合征中SPINK5基因剪接位点突变1例

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0012

E Erden, A C Ceylan, S Emre

{"title":"A New Splice-site Mutation of SPINK5 Gene in the Netherton Syndrome with Different Clinical Features: A Case Report.","authors":"E Erden, A C Ceylan, S Emre","doi":"10.2478/bjmg-2020-0012","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0012","url":null,"abstract":"Netherton syndrome (NS) is a rare genodermatosis characterized by the triad of ichthyosiform erythroderma, hair shaft abnormality and an atopic diathesis. We report a case of a 20-year-old male patient presented with pruritus, decreased sweat secretion and generalized erythema on his body. Netherton syndrome is caused by mutations in the SPINK5 gene that is a crucial role for epidermal barrier function in the skin. Different clinical and phenotypical features can occur based on various LEKTI-domains mutations. Diagnosis is made by the atopic story, hair shaft abnormality, cutaneous lesions and identification of the SPINK5 gene mutation. In our patient, we detected a new splice site mutation in the SPINK5 gene and pili annulati as hair abnormality. Affected patients are usually misdiagnosed because of cutaneous lesions such as atopic dermatitis. Therefore, each clinical finding should be evaluated together. We aimed to present a case with a new SPINK5 gene mutation and different clinical features in NS.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7c/7e/bjmg-23-091.PMC7474220.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

A Very Rare Partial Trisomy Syndrome: De Novo Duplication of 16q12.1q23.3 in a Turkish Girl with Developmental Delay and Facial Dysmorphic Features. 一种非常罕见的部分三体综合征:一名发育迟缓和面部畸形的土耳其女孩16q12.1q23.3基因从头重复。

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0009

A Türkyılmaz, O Yaralı

{"title":"A Very Rare Partial Trisomy Syndrome: De Novo Duplication of 16q12.1q23.3 in a Turkish Girl with Developmental Delay and Facial Dysmorphic Features.","authors":"A Türkyılmaz, O Yaralı","doi":"10.2478/bjmg-2020-0009","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0009","url":null,"abstract":"Trisomy 16 is the most common type of autosomal trisomy associated with spontaneous abortion and is incompatible with life. Upon examining previously reported cases of partial chromosome 16q duplication, it was noted that the majority of cases had complex chromosomal abnormalities due to parental balanced chromosomal translocation carriage. The clinical presentation of very rare pure partial trisomy 16q cases was associated with congenital anomalies, facial dysmorphic findings and intellectual disability. In this study, we evaluated the physical characteristics and genetic data of an 8-month-old girl with developmental delay and facial dysmorphic features. Dysmorphic features including prominent metopic suture, synophrys, asymmetric head shape, triangular and asymmetric face, telecanthus, epicanthal folds, down-slanting palpebral fissures, microphthalmia of the left eye, anteverted nares, smooth and tented philtrum, microretrognathia, low-set posteriorly rotated ears, auricular pits, high-arched palate, thin upper lip and hypotonia were recorded. Her karyotype was 46,XX,add(16)(q24). To identify the extension of the duplicated section, array comparative genomic hybridization (aCGH) analysis was performed, which showed a de novo 29.8 Mb duplication [arr[hgl9] 16q12.1q23.3(52459169-82285105) x 3], interpreted to be pathogenic. We present this case report to clarify the clinical findings of a rare chromosomal anomaly, discuss the genes that may be related to the phenotype and advance the literature in terms of knowledge regarding genotypephenotype correlation.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/d6/bjmg-23-103.PMC7474222.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38400484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

An Investigation of the COMT Gene Val158Met Polymorphism in Patients Admitted to the Emergency Department Because of Synthetic Cannabinoid Use. 急诊使用合成大麻素患者COMT基因Val158Met多态性研究

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0010

Y Nennicioglu, H Kaya, S Eraybar, S Atmaca, O Gorukmez, E Armagan

{"title":"An Investigation of the COMT Gene Val158Met Polymorphism in Patients Admitted to the Emergency Department Because of Synthetic Cannabinoid Use.","authors":"Y Nennicioglu, H Kaya, S Eraybar, S Atmaca, O Gorukmez, E Armagan","doi":"10.2478/bjmg-2020-0010","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0010","url":null,"abstract":"Catechol-O-methyl transferase (COMT) enzyme has a role in the inactivation of catecholamine neurotransmitters. Functional polymorphism in the COMT gene has been reported to play an important role in schizophrenia, bipolar affective disorder, aggressive and antisocial behavior, suicide attempts and the pathogenesis of Parkinson's disease. In this study, we aimed to investigate the effect of the Vall58Met polymorphism of the COMT gene on substance use, and treatment history in patients with synthetic cannabinoid (SC) intoxication. The COMT enzyme Val158Met polymorphisms from DNA of 49 patients who were evaluated in the Emergency Department after SC use and 50 healthy control groups aged 18-45 years, were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses as reported in the literature. Information regarding recurrent intake or hospitalization due to substance use was obtained from hospital records. Wild-type (WT) genotypes in 14 (28.6%) patients, heterozygous genotypes in 25 (51.0%) and homozygous genotypes in 10 (20.4%) patients were detected. Wild-type genotypes The homozygous genotype was found to be significantly higher in patients hospitalized due to drug addiction and substance use (p 0.008). The Vall58 Met polymorphism of the COMT gene was not found to be significant in the first use after substance intake, while a significant relationship was found in terms of this polymorphism in patients with substance addiction diagnosis and treatment history.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/c1/bjmg-23-063.PMC7474226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Relationship between Chromosomal Aberrations and Gene Expressions in the p53 Pathway in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病染色体畸变与p53通路基因表达的关系。

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0007

G Öztan, M Aktan, S Palanduz, H İşsever, S Öztürk, E Nikerel, A Uçur, G Bağatir, A Bayrak, K Çefle

{"title":"Relationship between Chromosomal Aberrations and Gene Expressions in the p53 Pathway in Chronic Lymphocytic Leukemia.","authors":"G Öztan, M Aktan, S Palanduz, H İşsever, S Öztürk, E Nikerel, A Uçur, G Bağatir, A Bayrak, K Çefle","doi":"10.2478/bjmg-2020-0007","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0007","url":null,"abstract":"Chronic lymphocytic leukemia (CLL) is a neoplasm characterized by excessive accumulation of B lymphocytes in the peripheral blood, bone marrow and lymph nodes. We assessed the expressions of 22 genes in the p53 pathway in 30 CLL patients and 15 healthy subjects by a RT2 Profiler PCR (polymerase chain reaction) Array technique and their relation to cytogenetic aberrations detected by fluorescent in situ hybridization (FISH). Our Student's t-test results indicated that ATM, ATR, BAX, CASP9, CDK4, CDKN2A, CHEK1, CHEK2, E2F3, MCL1, MDM2, MDM4, PCNA, RB1, P53 and BCL2 genes were statistically significant (p <0.001). For six genes (APAF1, CDKN1A, E2F1, GADD45A, PTEN and PTX3) were not statistically significant. The ATM, ATR, BAX, CASP9, CDK4, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, MDM4, PCNA, RB1, P53, E2F1, GADD45A and BCL2 genes were found to be upregulated by the 2-ᐃᐃCt (relative fold change in gene expression) method. The highest up-regulation was detected in CDKN2A and BCL2 genes, 10.22- and 8.51-fold, respectively. On the other hand, the PTX3 gene with a fold regulation of 1.84 was found to the highest downregulation. Overall, the CDNK2A BCL2 and PTX3 genes are related to the mechanism of the disease in the p53 pathway and may be an important predictor of the prognosis of the disease. The BCL2 gene may be associated with increased risk of developing CLL. We suggest that the PTX3 gene may be considered as a marker associated with CLL disease. The CDKN2A gene expression seems to play a protective role in CLL.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/cb/bjmg-23-015.PMC7474212.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

RANKL is a new Epigenetic Biomarker for the Vasomotor Symptom During Menopause. RANKL是绝经期血管舒缩症状的一种新的表观遗传生物标志物。

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0001

R Kalkan, M Altarda, O Tosun

{"title":"RANKL is a new Epigenetic Biomarker for the Vasomotor Symptom During Menopause.","authors":"R Kalkan, M Altarda, O Tosun","doi":"10.2478/bjmg-2020-0001","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0001","url":null,"abstract":"During menopausal transition, decreased level of estrogen brings a number of physiological problems and hormonal changes. In this study, promoter methylation of RANKL and FSHR genes were identified in 30 premenopausal and 35 postmenopausal women using methylation-specific high resolution melting (MS-HRM) analysis. The statistical analyses and their association with patient characteristics were performed by Pearson χ2 and Fisher's exact test (p <0.05). The methylated RANKL gene was detected in 16 postmenopausal cases, and 12 (75.0%) of the RANKL methylated cases had hot flashes (p = 0.024). The methylated FSHR gene was detected in 18 postmenopausal cases, and 13 (75.0%) of the methylated cases had hot flashes (p = 0.028). In vitro studies demonstrated the association between RANKL expression, FSH level and hot flashes in the mouse. Although lack of epigenetic studies in this field proves our results crucial and therefore, our results showed magnitude of epigenetic profiles of Turkish Cypriot post-menopausal women. This was the first study which has investigated the RANKL and FSHR methylation and their relationship with hot flashes in postmenopausal women.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/21/bjmg-23-051.PMC7474214.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

De Novo KMT2D Heterozygous Frameshift Deletion in a Newborn with a Congenital Heart Anomaly. 新生儿先天性心脏异常的新生KMT2D杂合移码缺失。

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0008

Š Stangler Herodež, N Marčun Varda, Kokalj Vokač N, D Krgović

{"title":"De Novo KMT2D Heterozygous Frameshift Deletion in a Newborn with a Congenital Heart Anomaly.","authors":"Š Stangler Herodež, N Marčun Varda, Kokalj Vokač N, D Krgović","doi":"10.2478/bjmg-2020-0008","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0008","url":null,"abstract":"Kabuki syndrome (KS) is characterized by typical facial features and patients are also affected by multiple congenital anomalies, of which congenital heart anomalies (CHAs) are present in 28.0 to 80.0%. In approximately 75.0% of patients, the genetic causes of KS are caused by mutation in the KMT2D gene. Although KS is a well-characterized syndrome, reaching the diagnosis in neonates is still challenging. Namely, newborns usually display mild facial features; therefore the diagnosis is mainly based on congenital malformations. In our case, a newborn was referred for next generation sequencing (NGS) testing due to the prenatally observed CHA. After birth, a ventricular septal defect (VSD), vesicoureteral reflux, muscular hypotonia, cleft palate, mild microcephaly, and some dysmorphic features, were noted. The NGS analysis was performed on the proband's genomic DNA using the TruSight One Sequencing Panel, which enriches exons of 4813 genes with clinical relevance to the disease. After variant calling, NGS data analysis was predominantly focused on rare variants in genes involved in VSD, microcephaly, and muscular hypotonia; features observed predominantly in our proband. With the aforementioned protocol, we were able to determine the previously unreported de novo frameshift deletion in the KMT2D gene resulting in translation termination. Although our proband is a typical representative of KS, his diagnosis was reached only after NGS analysis. Our proband thus represents the importance of genotypephenotype driven NGS analysis in diagnosis of patients with congenital anomalies.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/85/bjmg-23-083.PMC7474217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Ankyloblepharon-ectodermal Defects-cleft Lip-palate Syndrome Due to a Novel Missense Mutation in the SAM Domain of the TP63 Gene. 由TP63基因SAM结构域的新错义突变引起的强直性眼睑-外胚层缺陷-唇腭裂综合征。

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0013

M Tajir, J Lyahyai, S Guaoua, M El Alloussi, A Sefiani

{"title":"Ankyloblepharon-ectodermal Defects-cleft Lip-palate Syndrome Due to a Novel Missense Mutation in the SAM Domain of the TP63 Gene.","authors":"M Tajir, J Lyahyai, S Guaoua, M El Alloussi, A Sefiani","doi":"10.2478/bjmg-2020-0013","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0013","url":null,"abstract":"Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare genetic disease with an autosomal dominant transmission, characterized by several congenital anomalies. Clinical features include ectodermal defects affecting the skin, hair, teeth, nails and sweat glands, associated with typical eyelid fusion in addition to a cleft lip and/or palate. The diagnosis is based on clinical criteria and molecular genetic testing of TP63 gene, the gene related to AEC syndrome. In this context, most reported mutations induce an amino acid change in the sterile alpha motif (SAM) domain, and are predicted to disrupt protein-protein interactions. We here describe the case of a 2-year-old Moroccan girl diagnosed with AEC syndrome on the basis of clinical features. The molecular studies and bioinformatics tools revealed a novel heterozygous missense mutation c.1798G>C (p.Gly600Arg) in exon 14 of the TP63 gene, that was not found in her parents. The molecular analysis and the early diagnosis of this syndrome are important to offer appropriate genetic counseling and management to patients and their families.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/44/56/bjmg-23-095.PMC7474213.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells. 外源转录因子整合位点对诱导多能干细胞安全性和多能性的影响。

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2020-08-26 eCollection Date: 2020-06-01 DOI: 10.2478/bjmg-2020-0003

S Yin, W Li, G Yang, Y Cheng, Q Yi, S Fan, Q Ma, F Zeng

{"title":"Effect of Exogenous Transcription Factors Integration Sites on Safety and Pluripotency of Induced Pluripotent Stem Cells.","authors":"S Yin, W Li, G Yang, Y Cheng, Q Yi, S Fan, Q Ma, F Zeng","doi":"10.2478/bjmg-2020-0003","DOIUrl":"https://doi.org/10.2478/bjmg-2020-0003","url":null,"abstract":"Induced pluripotent stem cells (iPSCs), generated from somatic cells, not only possess similar characteristics with embryonic stem cells (ESCs), but also present more advantages than ESCs in medical applications. The classical induction method that utilizes the integration of exogenous genes into chromosomes may raise the potential risk of the safety of iPSCs. To investigate the potential correlation between the integration sites of exogenous transcription factors (TFs) and iPSCs' pluripotency and safety, the integration of exogenous genes in three iPSC lines, which met the golden standard of murine developmental assay (tetraploid complementation), were analyzed. Twenty-two integration sites of exogenous TFs were identified by nested inverse polymerase chain reaction (iPCR) and 39 flanking genes' functions were analyzed by gene ontology (GO). In the 22 integrated sites, 17 (77.3%) were located in the intergenic regions and the remainder were located in introns far from the transcription start sites. Microarray analysis of the flanking genes in these cells showed that there was no distinct difference in expression levels between the iPSCs, ESCs and mouse embryonic fibroblast (MEF), suggesting that the integration of exogenous TFs has no significant influence on the expression of flanking genes. Gene ontology analysis showed that although most of the flanking genes were housekeeping genes, which were necessary for basic life activity, none of these 39 flanking genes have correlation with tumorigenesis or embryogenesis, suggesting that the integration sites hold low risk of tumorigenesis.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/a1/bjmg-23-005.PMC7474223.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38402661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Basis of Inherited Colorectal Carcinomas in the Macedonian Population: An Update. 马其顿人口中遗传性结直肠癌的分子基础：最新进展。

IF 0.6 4区医学

Balkan Journal of Medical Genetics Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0027

M Staninova-Stojovska, N Matevska-Geskovska, M Panovski, B Angelovska, N Mitrevski, M Ristevski, R Jovanovic, A J Dimovski

{"title":"Molecular Basis of Inherited Colorectal Carcinomas in the Macedonian Population: An Update.","authors":"M Staninova-Stojovska, N Matevska-Geskovska, M Panovski, B Angelovska, N Mitrevski, M Ristevski, R Jovanovic, A J Dimovski","doi":"10.2478/bjmg-2019-0027","DOIUrl":"10.2478/bjmg-2019-0027","url":null,"abstract":"Hereditary factors are assumed to play a role in ~35.0-45.0% of all colorectal cancers (CRCs) with about 5.0-10.0% associated with high penetrant disease-causing mutations in genes correlated to hereditary polyposis (HP) or hereditary non polyposis syndromes (HNPCC). Although inherited germline mutations in mismatch repair (MMR) and the APC genes contribute significantly to CRC, genetic diagnosis cannot yet be obtained in more than 50.0% of familial cases. We present updated data of 107 probands from the Macedonian population with clinically diagnosed HP (n = 41) or HNPCC (n = 66) obtained by next generation sequencing (NGS) with three different gene panels covering the coding, flanking and promoter regions of 114 cancer predisposition genes. Using this approach, we were able to detect deleterious mutations in 65/107 (60.7%) patients, 50.4% of which were in known well-established CRC susceptibility genes and 10.2% in DNA repair genes (DRG). As expected, the highest frequencies of deleterious variants were detected in familial adenomatous polyposis (FAP) and in HNPCC patients with microsatellite instability (MSI) tumors (93.8 and 87.1%, respectively). Variants of unknown significance (VUS) were detected in 24/107 (22.4%) patients, mainly in HNPCC patients with microsatellite stable (MSS) tumors or patients with oligopolyposis. The majority of VUS were also found in DRG genes, indicating the potential role of a doble-strand brake DNA repair pathway deficiency in colorectal cancerogenesis. We could not detect any variant in 18/107 (16.8%) patients, which supports the genetic heterogeneity of hereditary CRC, particularly in HNPCC families with MSS tumors and in families with oligopolyposis.","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2019-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/66/bjmg-22-005.PMC6956642.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0