Balkan journal of medical genetics : BJMG最新文献

Results of Liquid Biopsy Studies by Next Generation Sequencing in Patients with Advanced Stage Non-small Cell Lung Cancer: Single Center Experience from Turkey. 下一代测序技术在晚期非小细胞肺癌患者中的液体活检研究结果:来自土耳其的单中心经验。

IF 0.6

Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0016

M Buyuksimsek, M Togun, Kara I Oguz, A Bisgin, I Boga, M Tohumcuoglu, A Ogul, Yetisir A Evren, B Sahin, Sumbul H Erdem, C Mirili

{"title":"Results of Liquid Biopsy Studies by Next Generation Sequencing in Patients with Advanced Stage Non-small Cell Lung Cancer: Single Center Experience from Turkey.","authors":"M Buyuksimsek, M Togun, Kara I Oguz, A Bisgin, I Boga, M Tohumcuoglu, A Ogul, Yetisir A Evren, B Sahin, Sumbul H Erdem, C Mirili","doi":"10.2478/bjmg-2019-0016","DOIUrl":"https://doi.org/10.2478/bjmg-2019-0016","url":null,"abstract":"Several studies demonstrated the utility of plasma-based cell-free circulating tumor DNA (ccfDNA) in determination of mutations in non-small cell lung cancer (NSCLC). We aimed to report our results of next generation sequencing (NGS) using liquid biopsy in patients with NSCLC. Patients with advanced stage NSCLC were enrolled and their genomic profiling results were recorded. Next generation sequencing targeted panel includes 19 hot-spot genes. The plasma was separated from the peripheral blood sample and ccfDNAs were isolated for NGS. We performed genomic profiling in 100 patients (20 females and 80 males) with a median age of 59.3 (range 26-79). A second liquid biopsy was performed in eight patients who developed progressive disease after the first treatment. The study population had adenocarcinoma (AC) (n = 73), squamous cell carcinoma (SCC) (n = 14), or NSCLC-NOS (not otherwise specified) (n = 13). In the SCC group, three of 14 patients had variants on EGFR and MET genes. In the AC and NSCLC-NOS groups, 39 out of 86 patients (45.3%) had variants. The most common one was in the EGFR gene (n = 27, 31.4%) including seven mutations related to drug resistance and two were polymorphisms. Three patients had both driver and resistance mutations (EGFR T790M, n = 2; KRAS exon 2 G12S and MET exon 14 E1012K, n = 1). Fifteen patients (17.4%) had an activating EGFR mutation and eight patients (9.3%) had variants in the KRAS gene. We reported our results regarding genomic profiling related to treatment using liquid biopsy in patients with NSCLC. Advantages of this method are the non invasiveness and reproducibility.","PeriodicalId":520567,"journal":{"name":"Balkan journal of medical genetics : BJMG","volume":" ","pages":"17-24"},"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/1a/90/bjmg-22-017.PMC6956641.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Evaluation of the JAK2V617F Mutational Burden in Patients with Philadelphia Chromosome Negative Myeloproliferative Neoplasms: A Single-center Experience. 费城染色体阴性骨髓增殖性肿瘤患者JAK2V617F突变负担的评估:单中心经验

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Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0021

M Popova-Labachevska, I Panovska-Stavridis, A Eftimov, Nestorovska A Kapedanovska, L Cevreska, M Ivanovski, N Ridova, S Trajkova, A J Dimovski

{"title":"Evaluation of the JAK2V617F Mutational Burden in Patients with Philadelphia Chromosome Negative Myeloproliferative Neoplasms: A Single-center Experience.","authors":"M Popova-Labachevska, I Panovska-Stavridis, A Eftimov, Nestorovska A Kapedanovska, L Cevreska, M Ivanovski, N Ridova, S Trajkova, A J Dimovski","doi":"10.2478/bjmg-2019-0021","DOIUrl":"https://doi.org/10.2478/bjmg-2019-0021","url":null,"abstract":"The identification of the JAK2V617F mutation in several distinct myeloproliferative neoplasms (MPNs) raised the question how one single mutation incites expression of at least three different clinical phenotypes, i.e., polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In order to further evaluate already published data on the correlation between mutant JAK2V617F allele burden and specific hematological and clinical parameters, we tested the level of the JAK2 mutation in 134 JAK2+ patients with different MPNs. The patients were diagnosed according to the 2008 WHO criteria and followed for a median of 48 months. The JAK2 V617F quantification was done with a real time polymerase chain reaction (real time-PCR) method. The median allele burden was lowest in ET (25.8%), followed by 34.6% in PV and 51.8% in PMF patients (p<0.01). There was statistically significant association between the mutational load of 10.0-50.0% and blood count parameters in the PV patients (p<0.05). In PMF patients the mutational load was in correlation with older age and leukocyte count that were higher in patients with the mutational load of 10.0-50.0% and >50.0% compared to those with a mutational load of <10.0%. There were no statistically significant associations between the allele burden and blood counts in the ET cohort. Our study confirmed an association between the JAK2V617F allele burden and the distinct MPN phenotypes, indicating unfavorable prognosis in patients with a higher JAK2 allele burden. Our results suggest that JAK2 quantification should be incorporated in the diagnostic work-up of MPN patients as a useful tool for optimal treatment decision.","PeriodicalId":520567,"journal":{"name":"Balkan journal of medical genetics : BJMG","volume":" ","pages":"31-36"},"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/3e/88/bjmg-22-031.PMC6956630.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Novel Genotype in Two Siblings with 5-α-reductase 2 Deficiency: Different Clinical Course due to the Time of Diagnosis. 5-α-还原酶2缺乏症兄弟姐妹的新基因型:因诊断时间不同而不同的临床病程

IF 0.6

Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0022

M Kocova, D Plaseska-Karanfilska, P Noveski, M Kuzmanovska

{"title":"Novel Genotype in Two Siblings with 5-α-reductase 2 Deficiency: Different Clinical Course due to the Time of Diagnosis.","authors":"M Kocova, D Plaseska-Karanfilska, P Noveski, M Kuzmanovska","doi":"10.2478/bjmg-2019-0022","DOIUrl":"https://doi.org/10.2478/bjmg-2019-0022","url":null,"abstract":"Steroid 5-α-reductase-2 (5-ARD) deficiency is a result of mutations of the SRD5A2 gene. It causes the disorder of sexual differentiation (DSD) in 46,XY individuals with a variable genital phenotype. We present two siblings with female external genitalia at birth and bilateral inguinal testes, raised as females. These are the first molecularly characterized patients from the Republic of North Macedonia (RN Macedonia) with a different clinical course due to the time of the diagnosis. Diagnosis of Patient 1 was based upon the detection of bilateral inguinal testes and testosterone/dihidrotestosterone ratio. Sex reversal was initiated by testes removal at the age of 20 months. Breast implantation and vaginoplasty were performed in adolescence and the girl is comfortable with the female sex. Her sibling, Patient 2, raised as a girl, was clinically assessed at 11.5 years due to the growth of phalus, deep voice and Adam's apple enlargement. No change of gender was accepted. Complex molecular analysis including multiplex quantitative fluorescent polymerase chain reaction (PCR) screening for sex chromosome aneuploidies and SRY presence, Sanger sequencing combined with multiplex ligation-dependent probe amplification (MLPA), microarray-based comparative genomic hybridization (aCGH), and real-time PCR analysis for detection of exon copy number changes confirmed a novel c.146C>A (p.Ala49Asp) point mutation in the first exon inherited from the mother, and complete deletion of the first exon and adjacent regions inherited from the father. Novel genotype causing 5-ARD is presented. Genetic analysis is useful for the diagnosis and timely gender assignment in patients with 5-ARD. However, final gender assignment is difficult and requires combined medical interventions.","PeriodicalId":520567,"journal":{"name":"Balkan journal of medical genetics : BJMG","volume":" ","pages":"69-76"},"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/18/bc/bjmg-22-069.PMC6956631.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Infantile Alexander Disease with Late Onset Infantile Spasms and Hypsarrhythmia. 小儿亚历山大病伴晚发性痉挛和心律失常。

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Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0017

J Paprocka, B Rzepka-Migut, N Rzepka, A Jezela-Stanek, E Morava

引用次数: 5

A Novel Splice-site Mutation on the MLC1 Gene Leading to Exon 9 Skipping and Megalencephalic Leukoencephalopathy with Subcortical Cysts in a Turkish Patient. 一种新的MLC1基因剪接位点突变导致外显子9跳变和伴有皮质下囊肿的巨脑白质脑病。

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Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0019

A Türkyılmaz, O Ünver, G Ekinci, D Türkdoğan

引用次数: 0

Association of Genetic Polymorphisms in the Matrix Gla Protein (MGP) Gene with Coronary Artery Disease and Serum MGP Levels. 基质玻璃蛋白(MGP)基因遗传多态性与冠状动脉疾病和血清MGP水平的关系

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Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0020

S Karsli-Ceppioglu, S Yazar, Y Keskin, M Karaca, N E Luleci, T Yurdun

{"title":"Association of Genetic Polymorphisms in the Matrix Gla Protein (MGP) Gene with Coronary Artery Disease and Serum MGP Levels.","authors":"S Karsli-Ceppioglu, S Yazar, Y Keskin, M Karaca, N E Luleci, T Yurdun","doi":"10.2478/bjmg-2019-0020","DOIUrl":"https://doi.org/10.2478/bjmg-2019-0020","url":null,"abstract":"Matrix Gla protein (MGP) is an important regulatory protein for inhibition of calcification in the vessel wall and cartilage. The MGP gene polymorphisms are suspected to increase the risk of extracellular calcification through altering the related gene expression and serum MGP levels. The goal of this study was to examine the correlation between rs4236 (Thr83-Ala), rs12304 (Glu60-X) and rs1800802 (T138-C) polymorphisms of the MGP gene and coronary artery calcification. Serum MGP levels of 168 subjects who had undergone coronary angiography were analyzed along with genotyping of MGP gene polymorphisms. The results indicated that serum MGP levels were significantly associated with rs4236 and rs1800802 polymorphisms of the MGP gene with the occurrence of coronary artery diseases (CAD). Allelic distributions of MGP gene polymorphisms and serum MGP levels, respectively, were not significantly interconnected with the presence of CAD. Our results revealed that serum MGP levels of CAD patients show association with rs4236 and rs1800802 polymorphisms, but serum MGP levels alone do not directly reflect the risk of CAD. The role of MGP genetic variants on formation and progression of arterial calcification should be regarded in cardiovascular diseases.","PeriodicalId":520567,"journal":{"name":"Balkan journal of medical genetics : BJMG","volume":" ","pages":"43-50"},"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/a3/da/bjmg-22-043.PMC6956629.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Otopalatodigital Syndrome Type I: Novel Characteristics and Prenatal Manifestations in two Siblings. I型指耳畸形综合征:两个兄弟姐妹的新特征和产前表现。

IF 0.6

Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0024

I Joksic, G Cuturilo, A Jurisic, S Djuricic, B Peterlin, M Mijovic, Orlic N Karadzov, A Egic, Z Milovanovic

{"title":"Otopalatodigital Syndrome Type I: Novel Characteristics and Prenatal Manifestations in two Siblings.","authors":"I Joksic, G Cuturilo, A Jurisic, S Djuricic, B Peterlin, M Mijovic, Orlic N Karadzov, A Egic, Z Milovanovic","doi":"10.2478/bjmg-2019-0024","DOIUrl":"https://doi.org/10.2478/bjmg-2019-0024","url":null,"abstract":"Otopalatodigital spectrum disorder (OPDSD) is rare group of X-linked disorders caused by mutations in the filamin A (FLNA) gene. It is characterized by skeletal dysplasia of variable severity and different extra skeletal manifestations. Its presentation in the fetal period is quite unspecific, so diagnosis is usually made after birth. We present prenatal ultrasonography and postmortem findings that led us to a diagnosis of the mildest form of OPDSD (OPD type I) in two consecutive pregnancies. This is the first report on prenatal diagnosis (PND) of OPD type I. Affected fetuses showed facial dysmorphy (hypertelorism, micrognathia, cleft palate) and digital anomalies, features typical of OPD type I. In addition, microphtalmia and early neonatal death due to severe respiratory distress syndrome are described as a novel characteristics of the disorder. Clinical exome sequencing revealed a hemizygous missense pathogenic variant in the FLNA gene (NM_ 001110556.1: c.620C>T). We suggest that the presence of hypertelorism, micrognathia, digital anomalies on prenatal ultrasound examination should alert suspicion to OPDSD. Detailed clinical examination of mother and other female relatives is of great importance in establishing definitive diagnosis of OPD type I.","PeriodicalId":520567,"journal":{"name":"Balkan journal of medical genetics : BJMG","volume":" ","pages":"83-88"},"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/ed/cc/bjmg-22-083.PMC6956634.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Clinical Next Generation Sequencing Reveals an H3F3A Gene as a New Potential Gene Candidate for Microcephaly Associated with Severe Developmental Delay, Intellectual Disability and Growth Retardation. 临床下一代测序揭示H3F3A基因是严重发育迟缓、智力残疾和生长迟缓相关的小头症的新潜在候选基因

IF 0.6

Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0028

A Maver, G Čuturilo, Stojanović J Ruml, B Peterlin

{"title":"Clinical Next Generation Sequencing Reveals an H3F3A Gene as a New Potential Gene Candidate for Microcephaly Associated with Severe Developmental Delay, Intellectual Disability and Growth Retardation.","authors":"A Maver, G Čuturilo, Stojanović J Ruml, B Peterlin","doi":"10.2478/bjmg-2019-0028","DOIUrl":"https://doi.org/10.2478/bjmg-2019-0028","url":null,"abstract":"Microcephaly is characterized by significant clinical and genetic heterogeneity, therefore reaching the genetic diagnosis remains challenging in this group of disorders. We describe a case of a girl with secondary microcephaly, associated with severe developmental delay, intellectual disability, growth retardation and dysmorphic features. For purposes of clinical genetic diagnostic testing, we performed trio whole exome sequencing in the proband and unaffected parents. We found a heterozygous de novo missense variant in the H3F3A gene in the proband (NM_ 002107.4: c.185T>G), which is absent from the gnomAD and from the Slovenian Genome databases. The identified variant affects a highly conserved leucine residue at position 62 of the histone H3 protein (H3.3) and is predicted to affect the physicochemical properties of the affected protein. Mouse models, which demonstrated involvement of H3.3 protein in the control of neuronal- and glial-specific gene expression patterns that control synaptic connectivity and behavioral plasticity. Additionally, we also identified similar cases reported in the ClinVar database. These arguments support the possible pathogenic role of the reported genetic variant and thus suggest a novel molecular mechanism for this syndromic form of microcephaly.","PeriodicalId":520567,"journal":{"name":"Balkan journal of medical genetics : BJMG","volume":" ","pages":"65-68"},"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/31/99/bjmg-22-065.PMC6956640.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

A 7-year-old Boy with Hand Tremors and a Novel Mutation for L-2-hydroxyglutaric Aciduria. 1例7岁男童手部震颤及l -2-羟基戊二酸尿新突变。

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Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0015

A Olgac, Orgun L Tekin, F S Ezgü, G Biberoǧlu, L Tümer

引用次数: 6

Chronic Obstructive Pulmonary Disease Risk and Smoking Cessation Changes Induced by CHRNA5-A3 and CHRNB3-A6 Variation in a Chinese Male Population. 中国男性人群CHRNA5-A3和CHRNB3-A6变异诱导的慢性阻塞性肺疾病风险和戒烟变化

IF 0.6

Balkan journal of medical genetics : BJMG Pub Date : 2019-12-21 eCollection Date: 2019-12-01 DOI: 10.2478/bjmg-2019-0018

L Zhao, L-Y Zou, B-F Cheng, X-J Yu, J-H Zou, W Han

{"title":"Chronic Obstructive Pulmonary Disease Risk and Smoking Cessation Changes Induced by CHRNA5-A3 and CHRNB3-A6 Variation in a Chinese Male Population.","authors":"L Zhao, L-Y Zou, B-F Cheng, X-J Yu, J-H Zou, W Han","doi":"10.2478/bjmg-2019-0018","DOIUrl":"https://doi.org/10.2478/bjmg-2019-0018","url":null,"abstract":"Most studies in the field of CHRNA5-A3 and CHRNB3-A6 have only focused on lung cancer risk; however, the associations with chronic obstructive pulmonary disease (COPD) risk and smoking cessation is less understood, particularly in the Chinese male population. In this study, samples from 823 male patients with COPD (non smokers: 416; still smoking: 407) and 435 smoking male healthy control subjects were performed with DNA extraction and single nucleotide polymorphism (SNP) genotyping. We studied three SNPS in two genes, namely rs667282 and rs3743073 in CHRNA5-A3 and rs4950 in CHRNB3-A6, and their distributions in the three groups are not statistically different (p >0.05). We grouped COPD patients according to whether they had successfully quit smoking, the CT genotype of rs667282 demonstrated association with an increased rate of successful smoking cessation compared with the TT genotype [adjusted odds ratio (OR) = 0.54, 95% confidence interval (95% CI) = 0.37-0.7, p <0.001); rs4950 AG genotypes were distinctly associated with increased rates of successful smoking cessation (adjusted OR = 0.55, 95% CI = 0.40-0.76, p <0.001). The effect is significant under the assumption of an over dominant mode of inheritance (adjusted OR = 0.58, 95% CI = 0.43 to 0.79, p <0.001). No significant difference in rs3743073 was found (p >0.05). Our findings confirmed the hypothesis that CHRNA5-A3 and CHRNB3-A6 variation are not associated with the risk of COPD. We found CHRNA5-A3 and CHRNB3-A6 were significantly associated with successful smoking cessation in smoking COPD patients.","PeriodicalId":520567,"journal":{"name":"Balkan journal of medical genetics : BJMG","volume":" ","pages":"51-58"},"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/33/f4/bjmg-22-051.PMC6956637.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0