rss_2.0Balkan Journal of Medical Genetics FeedSciendo RSS Feed for Balkan Journal of Medical Geneticshttps://sciendo.com/journal/BJMGhttps://www.sciendo.comBalkan Journal of Medical Genetics Feedhttps://sciendo-parsed.s3.eu-central-1.amazonaws.com/6470de7f71e4585e08aa75ca/cover-image.jpghttps://sciendo.com/journal/BJMG140216Association of rs35006907 Polymorphism with Risk of Dilated Cardiomyopathy in Han Chinese Populationhttps://sciendo.com/article/10.2478/bjmg-2023-0004<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Several investigations have demonstrated the association of <italic>MTSS1</italic> with left ventricular (LV) structure and function. A recently published study has even revealed that rs35006907 was associated with both <italic>MTSS1</italic> expression and the risk of dilated cardiomyopathy (DCM).</p> </sec> <sec><title style='display:none'>Objective</title> <p>Our study intended to investigate the relationship between rs35006907 and the risk of DCM in the Han Chinese population.</p> </sec> <sec><title style='display:none'>Methods</title> <p>A total of 529 DCM and 600 healthy controls were recruited. We conducted genotyping for rs35006907 in all participants. Gene association studies were performed to assess the association between rs35006907 and the risk of DCM. A series of functional assays including western blot, realtime PCR and firefly luciferase reporter gene assays were conducted to illuminate the underlying mechanism.</p> </sec> <sec><title style='display:none'>Results</title> <p>We found that rs35006907-A allele was significantly associated with reduced risk of DCM in additive (p= 0.004; OR=0.78; 95% CI=0.66–0.93) and recessive models (p= 0.0005; OR=0.56; 95%CI=0.41–0.78) when compared with the rs35006907-C allele. There were significant differences in the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) between rs35006907-CC/AC and AA genotypes. Furthermore, the variant rs35006907-A allele presented lower reporter gene activity, reduced mRNA and protein expression levels when compared with the C allele.</p> </sec> <sec><title style='display:none'>Conclusions</title> <p>Our findings demonstrated that rs35006907-C allele increased the risk of DCM in Han Chinese population. Besides, rs35006907-C displayed higher reporter gene activity and increased <italic>MTSS1</italic> expression in human samples.</p> </sec> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00042023-07-31T00:00:00.000+00:00Difficulties in Diagnosing Fabry Disease in Patients with Unexplained Left Ventricular Hypertrophy (LVH): Is the Novel GLA Gene Mutation a Pathogenic Mutation or Polymorphism?https://sciendo.com/article/10.2478/bjmg-2023-0010<abstract> <title style='display:none'>Abstract</title> <p>Fabry disease (FD) is an X-linked, lysosomal glycosphingolipid storage disorder that occurs very rarely. Cardiac involvement may comprise of left ventricular hypertrophy (LVH), arrhythmias, conduction abnormalities, heart failure and valvular abnormalities. The goal of this study was to conduct gene analysis for FD in patients suffering from unexplained LVH. 120 patients over the age of 30 who were diagnosed by echocardiography with idiopathic LVH were included in the study. Patients with severe hypertension, intermediate valve disease such as moderate aortic stenosis, known FD, and a family history of autosomal dominant hypertrophic cardiomyopathy were excluded from the study. <italic>GLA</italic> gene mutations were studied by Sanger sequence analysis in all patients. Of the 120 total patients included in this study, 69 were female (58%) and 51 were male (42%). The mean age was 60.3 ± 15.7. <italic>GLA</italic> gene mutations were detected in three male patients. The detected mutations are as follows: <italic>NM_000169.2:IVS6-10G&gt;A (c.1000–10G&gt;A), NM_000169.2:c.937G&gt;T (p.D313Y) (p.Asp313Tyr)</italic> and <italic>NM_000169.2:c.941A&gt;T (p.K314M) (p.Lys314Met)</italic>. Early diagnosis is of vital importance in FD, which can be treated with enzyme replacement. Genetic screening in patients diagnosed with idiopathic LVH by echocardiography is important in the early diagnosis and treatment of FD. Patients over 30 years of age with idiopathic LVH should be screened for FD. Various new polymorphisms can be detected in genetic screening. Identifying new polymorphisms is important for knowing the true mutations in FD.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00102023-07-31T00:00:00.000+00:00Androgen Insensitivity Syndrome DUE to Non-Coding Variation in the Androgen Receptor Gene: Review of the Literature and Case Report of a Patient with Mosaic c.-547C>T Varianthttps://sciendo.com/article/10.2478/bjmg-2023-0012<abstract> <title style='display:none'>Abstract</title> <p>Sexual development (SD) is a complex process with strict spatiotemporal regulation of gene expression. Despite advancements in molecular diagnostics, disorders of sexual development (DSD) have a diagnostic rate of ~50%. Androgen insensitivity syndrome (AIS) represents the most common form of 46,XY DSD, with a spectrum of defects in androgen action. Considering the importance of very strict regulation of the SD, it is reasonable to assume that the genetic cause for proportion of the DSD lies in the non-coding part of the genome that regulates proper gene functioning. Here we present a patient with partial AIS (PAIS) due to a mosaic <italic>de novo</italic> c.-547C&gt;T pathogenic variant in the 5′UTR of androgen receptor (<italic>AR</italic>) gene. The same mutation was previously described as inherited, in two unrelated patients with complete AIS (CAIS). Thus, our case further confirms the previous findings that variable gene expressivity could be attributed to mosaicism. Mutations in 5′UTR could create new upstream open reading frames (uORFs) or could disrupt the existing one. A recent systematic genome-wide study identified <italic>AR</italic> as a member of a subset of genes where modifications of uORFs represents an important disease mechanism. Only a small number of studies are reporting non-coding mutations in the <italic>AR</italic> gene and our case emphasizes the importance of molecular testing of the entire <italic>AR</italic> locus in AIS patients. The introduction of new methods for comprehensive molecular testing in routine genetic diagnosis, accompanied with new tools for in sillico analysis could improve the genetic diagnosis of AIS, and DSD in general.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00122023-07-31T00:00:00.000+00:00Polyploidy Phenomenon as a Cause of Early Miscarriages in Abortion Materialshttps://sciendo.com/article/10.2478/bjmg-2023-0002<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Objectives</title> <p>Chromosomal abnormalities are an important cause of especially early miscarriages. The aim of this study was to analyze the chromosomal aberrations and determine the frequencies of numerical and structural chromosome abnormalities in spontaneous abortion materials.</p> </sec> <sec><title style='display:none'>Methods</title> <p>This was a prospective research and ninety two abortion samples obtained from women who had one or more miscarriages were included in the study. Conventional karyotype analysis was performed on each sample to identify possible chromosomal abnormalities.</p> </sec> <sec><title style='display:none'>Results</title> <p>By karyotype analysis, 11 polyploidy cases, (9 triploids and 2 tetraploids), 8 trisomies (one of which was mosaic), 2 monosomies (monosomy X), 1 isochromosome, 1 Xq deletion, and 4 translocations were detected in abortion materials. Isochromosome and Xq deletion cases were also mosaic. In addition, five polymorphic variants were revealed. We found higher paternal age in polyploidy cases.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>The most common anomaly we found in abortion materials was polyploidy. This was followed by aneuploidy (trisomy and monosomy). Polyploidy (triploidy or tetraploidy) emerged as an important cause in cases of spontaneous abortion. Paternal age may be associated with polyploidy especially triploidy.</p> </sec> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00022023-07-31T00:00:00.000+00:00Prognostic Value of (rs2069514 and rs762551) Polymorphisms in COVID-19 Patientshttps://sciendo.com/article/10.2478/bjmg-2023-0005<abstract> <title style='display:none'>Abstract</title> <p>The aim of the study was to examine the genotype-allele determination of <italic>CYP1A2</italic> rs2069514 and rs762551 polymorphisms in patients with mild and severe COVID-19 and to determine their effectiveness as prognostic criteria in COVID-19. The study consists of 60 patients who were hospitalized in intensive care or outpatient treatment due to COVID-19 in Istanbul NP Brain Hospital between 2020–2021. Genotyping was conducted by Real-Time PCR. Age (p&lt;0.001); chronic disease (p=0.002); cardiovascular disease (p=0.004); respiratory distress (p&lt;0.001); neurological disease (p=0.004); fatigue (p=0.048); loss of taste and smell (p=0.003); nausea/vomiting (p=0.026); intubated (p&lt;0.001); ground glass image (p&lt;0.001) and <italic>CYP1A2</italic> genotypes (p&lt;0.001) showed a statistically significant difference between patients with and without intensive care admission. According to multivariate logistic regression analysis, <italic>CYP1A2</italic> *1A/*1C + *1C/*1C genotypes (OR:5.23 95% CI: 1.22–22.36; p=0.025), chronic disease (OR:4.68 95% CI:1.14–19.15; p=0.032) or patients at 65 years or older (OR:5.17, 95%CI:1.26–21.14; p=0.022) increased the risk of admission to the intensive care unit. According to our results, we strongly suggest considering the <italic>CYP1A2</italic> rs2069514 and rs762551 polymorphisms as important predictors of Intensive Care Unit admission in patients with COVID-19, and we also suggest that genotype results will guide clinicians for the benefit and the efficiency of the treatment.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00052023-07-31T00:00:00.000+00:00Preventable Hazards from in Vitro Fertilization – A Case Series of CF Patients from Bulgariahttps://sciendo.com/article/10.2478/bjmg-2023-0001<abstract> <title style='display:none'>Abstract</title> <p>Pre-implantation genetic diagnosis (PGD) is not often performed when donor gametes are used, due to its high cost. This is with the presumption that the donors are healthy.</p> <p>We report on five cases of babies with confirmed cystic fibrosis (CF), being the result from in vitro fertilization (IVF) with donor (4 cases) or own gametes (one case). There has been no family history for CF in any of the families affected. The clinical presentation in the children ranged from meconium ileus to recurrent respiratory infections and severe nasal polyposis. The age of diagnosis also varied from birth until 9 years.</p> <p>Since one of the presented cases was discovered in a very renowned private IVF clinic, the clinic changed their own protocol, and currently they test every donor for CF carriership. The percentage of CF carriers in the donor population is roughly the same as the one predicted in the general population of Bulgaria – 1/33.</p> <p>Although PGD is costly, the costs for proper care for a CF patient are currently much higher. The more economical option would to screen every donor for CF carriership.</p> <p>IVF requires a lot of physical and psychological stamina. The couples that go through this procedure also require a great deal of hope. It is essential to be more preconscious for possible congenital diseases.</p> <p>We advocate every IVF center to test the donors for CF carriership or to provide PGD for their clients.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00012023-07-31T00:00:00.000+00:00Features of the Wolf-Hirschhorn Syndrome (WHS) from Infant to Young Teenagerhttps://sciendo.com/article/10.2478/bjmg-2023-0006<abstract> <title style='display:none'>Abstract</title> <p>Wolf-Hirschhorn syndrome is a rare condition caused by terminal deletions, of variable size, in the short arm of chromosome 4. The syndrome displays the combination of typical morphological facial variations, intellectual disability, language delay, and various malformations. This report describes the clinical aspect and developmental evolution of a male patient with Wolf-Hirschhorn syndrome, from infancy to adolescence. The patient was first examined and diagnosed at 11 months, with follow-up at the ages of 4 and 16.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00062023-07-31T00:00:00.000+00:00Two Brothers from Macedonia with Gitelman Syndromehttps://sciendo.com/article/10.2478/bjmg-2023-0009<abstract> <title style='display:none'>Abstract</title> <p>Gitelman syndrome (GS) is a rare renal tubulopathy with an autosomal recessive mode of inheritance, caused by biallelic pathogenic variants in the <italic>SLC12A3</italic> gene. The clinical features may overlap with other disorders, such as Bartter syndrome type 3, HNF1B nephropathy or even mitochondrial disease, but can be distinguished by molecular genetic analysis.</p> <p>Here we report on two preschool brothers, who presented with a several months’ history of episodes of carpopedal spasms and muscle aches.</p> <p>The biochemical analyses revealed hypokalemia and hypomagnesemia without metabolic alkalosis. A 24-h urine sample demonstrated hypocalciuria.</p> <p>The molecular analyses showed that both patients were heterozygous for 3 (likely) pathogenic variants in <italic>SLC12A3</italic>: c.1805_1806del; p. (Tyr602Cysfs*31), c.2660+1G&gt;A and c.2944 A&gt;T; p. (Ile982Phe). Analysis of the parents showed that the mother was heterozygous for the c.2944 A&gt;T p.(Ile982Phe) variant, and the father carried the other 2 variants (c.1805_1806del and c.2660+1G&gt;A).</p> <p>Herein we present two children in a family from N. Macedonia with clinical manifestations and electrolyte imbalances suggestive of GS. The results of the tubulopathy next generation sequencing (NGS) panel confirmed the diagnosis. The boys are treated with a high salt diet and oral potassium and magnesium supplements.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00092023-07-31T00:00:00.000+00:00Differentially Expressed Circulating Long-Noncoding RNAS in Premature Infants with Respiratory Distress Syndromehttps://sciendo.com/article/10.2478/bjmg-2023-0011<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Purpose</title> <p>Recent studies have addressed the association between lung development and long-noncoding RNAs (lncRNAs). But few studies have investigated the role of lncRNAs in neonatal respiratory distress syndrome (RDS). Thus, this study aimed to compare the expression profile of circulating lncRNAs between RDS infants and controls.</p> </sec> <sec><title style='display:none'>Methods</title> <p>10 RDS infants and 5 controls were enrolled. RDS patients were further divided into mild and severe RDS subgroups. Blood samples were collected for the lncRNA expression profile. Subsequently, differentially expressed lncRNAs were screened out. Bioinformatics analysis was applied to establish a co-expression network of differential lncRNAs and mRNAs, and predict the underlying biological functions.</p> </sec> <sec><title style='display:none'>Results</title> <p>A total of 135 differentially expressed lncRNAs were identified, including 108 upregulated and 27 downregulated lncRNAs (fold-change&gt;2 and <italic>P</italic>&lt;0.05) among the three groups (non-RDS, mild RDS and severe RDS groups). Of these lncRNAs, four were selected as showing higher fold changes and validated by qRT-PCR. ENST00000470527.1, ENST00000504497.1, ENST00000417781.5, and ENST00000440408.5 were increased not only in the plasma of total RDS patients but also in the severe RDS subgroup. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses showed that differentially expressed lncRNAs may play important roles in RDS through regulating PI3KAkt, RAS, MAPK, and TGF-β signaling pathways.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>The present results found that ENST00000470527.1, ENST00000504497.1, ENST00000417781.5, and ENST00000440408.5 may be invol ved in RDS. This could provide new insight into research of the potential pathophysiological mechanisms of preterm RDS.</p> </sec> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00112023-07-31T00:00:00.000+00:00Sensorineural Hearing Loss in a Child with Succinic Semialdehyde Dehydrogenase Deficiencyhttps://sciendo.com/article/10.2478/bjmg-2023-0008<abstract> <title style='display:none'>Abstract</title> <p>Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal-recessive disorder of gamma-aminobutyric acid (GABA) metabolism, resulting in accumulation of GABA and gamma-hydroxybutyric acid (GHB) in physiological fluids. Approximately 450 patients have been diagnosed worldwide with this inherited neurotransmitter disorder. We report on a five-year-old male patient, homozygous for the pathogenic variant (NM_170740:c.1265G&gt;A) in <italic>ALDH5A1</italic> presenting with an unexpected association of typical SSADH deficiency manifestations with bilateral sensorineural hearing loss (SNHL). Brainstem evoked response audiometry (BERA) testing showed mid-frequency sensorineural hearing damage that suggested a hereditary component to SNHL. Whole exome sequencing (WES) failed to discern other genetic causes of deafness. Several variants of uncertain significance (VUS) detected in genes known for their role in hearing physiology could not be verified as the cause for the SNHL. It is known that central auditory processing depends on a delicate balance between excitatory and inhibitory neurotransmission, and GABA is known to play a significant role in this process. Additionally, excessive concentrations of accumulated GABA and GBH are known to cause a down-regulation of GABA receptors, which could have an adverse influence on hearing function. However, these mechanisms are very speculative in context of SNHL in a patient with inherited disorder of GABA metabolism. Injury of the globi pallidi, one of hallmarks of SSADH deficiency, could also be a contributory factor to SNHL, as was suspected in some other inborn errors in metabolism. We hope that this case will contribute to the understanding of phenotypic complexity of SSADH deficiency.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00082023-07-31T00:00:00.000+00:00The Predisposition for Type 2 Diabetes Mellitus and Metabolic Syndromehttps://sciendo.com/article/10.2478/bjmg-2023-0003<abstract> <title style='display:none'>Abstract</title> <p>Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are diseases caused by the interaction of genetic and non-genetic factors. Therefore, the aim of our study was to investigate the association between six common genetic polymorphisms and T2DM and MetS in males. A total of 120 T2DM, 75 MetS, and 120 healthy controls (HC) were included in the study. <italic>ACE</italic> ID, <italic>eNOS</italic> 4a/b, <italic>ATR1</italic> A1166C, <italic>OXTR</italic> (A&gt;G), <italic>SOD1</italic> +35A/C, <italic>CAT</italic>-21A/T gene polymorphisms were genotyped by PCR or PCR-RFLP techniques. T2DM was diagnosed at an earlier age compared to MetS (54 vs 55 years old, p=0.0003) and the difference was greater in carriers of the <italic>OXTR</italic> G allele (54 vs 56 years old, p=0.0002) or both <italic>OXTR</italic> G and <italic>eNOS</italic> b alleles (54 vs 56, p=0.00016). The <italic>SOD1</italic> AA genotype (O.R.=0.11, p=0.0006) and the presence of both <italic>ACE</italic> I and <italic>OXTR1</italic> A (O.R.=0.39, p=0.0005) alleles revealed to be protective for T2DM. <italic>SOD1</italic> AA and AC genotypes were protective factors for triglyceride (p=0.0002 and p=0.0005, respectively) and HDL cholesterol (p=0.0002 and p=0.0004, respectively) levels in T2DM patients. <italic>ACE</italic> DD was identified more frequently in hypertensive T2DM patients (O.R.=3.77, p=0.0005) and in those who reported drinking alcohol (p=0.0001) comparing to HC and T2DM patients who did not drink alcohol, respectively. We observed that T2DM patients who reported drinking alcohol had an increased frequency of <italic>ACE</italic> DD and <italic>eNOS</italic> bb (p&lt;0.0001), or <italic>ACE</italic> DD and <italic>OXTR</italic> G (p&lt;0.0001) compared to non-drinkers. No gene polymorphisms were associated with MetS.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00032023-07-31T00:00:00.000+00:00Non-Invasive Screening Test Paradox in a Case Born with Mixed Gonadal Dysgenesis (45,X/46,Xy)https://sciendo.com/article/10.2478/bjmg-2023-0007<abstract> <title style='display:none'>Abstract</title> <p>Noninvasive prenatal testing (NIPT) is commonly used to screen for fetal trisomy 13, 18, and 21 and often for sex chromosomal aneuploidies (SCAs). Although the testing is also used for sex chromosomal aneuploidies, it is not as efficient as it is for common trisomies. In this particular study, we present a case for whom the NIPT diagnosis was originally 45,X and who was diagnosed with mixed gonadal dysgenesis 45,X/46,XY after birth. A 38-year-old [G3P3] pregnant woman underwent NIPT at 15 weeks’ gestation and was found to be at probable risk for 45,X. Because cordocentesis is an invasive procedure, the pregnant woman did not want to undergo cordocentesis. Consequently, postnatal cytogenetic analysis was performed and the baby’s karyotype was shown to be 45,X/46,X,+mar?. No numerical and/or structural anomalies were observed in the karyotypes of parents and siblings. Based on the microarray analysis of the analyzed sample, one copy of the X chromosome was detected in all cells and the presence of one copy of the Y chromosome was detected in a ~40% mosaic state: arr(X) x1,(Y)x1[0.4]. <italic>SRY</italic> gene duplication on Y chromosome was confirmed by fluorescence in situ hybridization (FISH) and microarray analysis. The patient’s clinical examination showed ambiguous genitalia (clitoromegaly) and dysmorphic facial features. The baby underwent surgery for aortic coarctation. The results were consistent with a genetic diagnosis of 45,X/46,XY mixed gonadal dysgenesis. Genetic counselling was offered to the family. In conclusion, NIPT still has potential limitations in correctly identifying sex chromosomes and mosaicism that may mislead clinicians and families.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2023-00072023-07-31T00:00:00.000+00:00 Related Diastrophic Dysplasia in 42-Years Ukrainian Womenhttps://sciendo.com/article/10.2478/bjmg-2022-0018<abstract> <title style='display:none'>ABSTRACT</title> <p>Diastrophic dysplasia (DTD) is an uncommon pathology which falls under the group of skeletal dysplasias with its first symptoms observed from birth. The pathology is often featured by short stature and abnormally short extremities (also known as short-limbed dwarfism); the osseous structures of the body (bones and joints) are characterized through defective development in many body regions. More than 300 genes were reported to be involved in DTD etiology with autosomal recessive, autosomal dominant and X-linked manner.</p> <p>We describe clinical case of a 42-year-old woman from the west of Ukraine with diastrophic dysplasia and two pathogenic variants <italic>c.1020_1022del (p.Val341del)</italic> and <italic>c.1957T&gt;A (p.Cys653Ser)</italic> identified in <italic>SLC26A2</italic> gene.</p> <p>SLC26A2-related diastrophic dysplasia<bold/> was confirmed<bold/> based on the presence of pathogenic variants in <italic>SLC26A2</italic>, which is associated with autosomal recessive forms of skeletal dysplasia, combined with phenotypic symptoms and radiographic findings.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00182023-05-02T00:00:00.000+00:00KDM3A, a Novel Blood-Based Biomarker in Colorectal Carcinogenesishttps://sciendo.com/article/10.2478/bjmg-2022-0021<abstract> <title style='display:none'>ABSTRACT</title> <p>Colorectal cancer (CRC) is one of the leading causes of cancer-linked deaths globally. The determination of biomarkers is important in the prognosis and treatment of CRC. Previous studies emphasized the relationship between hypoxia and CRC in humans, and there is strong evidence that this process is strongly related to HIF-1. KDM3A is a histone demethylase that could directly bind to HIF-1α, a subunit of HIF-1. This study aimed to reveal whether the expression level of the <italic>KDM3A</italic> gene could be used as a predictor of CRC. The expression levels of <italic>HIF-1α, KDM3A</italic>, and Epithelial-Mesenchymal Transition (EMT) genes were evaluated by qRT-PCR in leukocyte samples of 50 CRC patients in different stages and 50 healthy controls. <italic>HIF-1α</italic> and <italic>KDM3A</italic> expression levels were significantly higher in the CRC group, compared to the controls. <italic>Slug</italic> and <italic>ZEB-1</italic> genes, the mesenchymal markers, showed the same significance pattern between groups. We acquired 0.664 AUC with 54% sensitivity and 85.4% specificity for separating controls from CRC patients by using the <italic>KDM3A</italic> expression levels in ROC analysis. This data support that <italic>KDM3A</italic> could be a novel supplementary biomarker in diagnosis of CRC, which could be noninvasively detected in circulation.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00212023-05-02T00:00:00.000+00:00High Risk of Gestational Trophoblastic Neoplasia Development in Recurrent Hydatidiform Moles with Pathogenic Variationshttps://sciendo.com/article/10.2478/bjmg-2022-0025<abstract> <title style='display:none'>ABSTRACT</title> <sec> <title style='display:none'>Objective</title> <p>Pathogenic variations of the <italic>NLRP7</italic> and <italic>KHDC3L</italic> genes are responsible for familial recurrent hydatidiform moles, a rare autosomal recessive phenomenon that can lead to severe comorbidities. Little is known about the diversity of genetic defects or the natural course of disease progression among recurrent hydatidiform mole cases from distinct ethnicities. In this study, we aimed to investigate the mutation profile and pregnancy outcomes in patients with multiple molar pregnancies.</p> </sec> <sec> <title style='display:none'>Material and Methods</title> <p>Three unrelated cases with recurrent molar pregnancies are included in this study. None of the patients had a known family history of molar pregnancy. Clinical findings and follow-up results are documented. Sanger sequencing is used to reveal genetic defects in exons and exon-intron boundaries of <italic>NLRP7</italic> and <italic>KHDC3L</italic> genes.</p> </sec> <sec> <title style='display:none'>Results</title> <p><italic>NLRP7</italic> pathogenic variants were found in all three cases. In two cases, homozygous, c.2471+1G&gt;A canonical splice cite variant was identified and in one case a homozygous, c.2571dupC (p.Ile858HisfsTer11) frameshift variant was identified. No variant in the <italic>KHDC3L</italic> gene was found in any case. In all cases, the development of gestational trophoblastic neoplasia complicated the clinical course and the treatment plans.</p> </sec> <sec> <title style='display:none'>Conclusions</title> <p>We found that defects of the <italic>NLRP7</italic> gene are principally responsible for etiology in our region, and the mutation profile suggests a founder effect in the Turkish population. We suggest early genetic diagnosis and counseling in molar pregnancies and recommend close follow-up in terms of conversion to gestational trophoblastic neoplasia.</p> </sec> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00252023-05-02T00:00:00.000+00:00Molecular Characterization of Microrna Interference and Aristolochic Acid Intoxication Found in Upper Tract Urothelial Carcinoma in Patients with Balkan Endemic Nephropathy: A Systematic Review of the Current Literaturehttps://sciendo.com/article/10.2478/bjmg-2022-0027<abstract> <title style='display:none'>ABSTRACT</title> <p>The term “aristolochic acid nephropathy” (AAN) is used to include any form of toxic interstitial nephropathy that is caused either by ingestion of plants containing aristolochic acids (AA) or by the environmental contaminants in food such as in Balkan endemic nephropathy (BEN). Aristolochic acid (AA) intoxication is strongly associated with the development of upper tract urothelial carcinoma (UTUC); however, the underlying molecular mechanism remains to be defined. MicroRNAs (miRNA) regulate several biological processes, including cell proliferation, differentiation, and metabolism, acting as oncogenes or tumor suppressors. A unique miRNA expression profile suggested that miRNAs could function as regulators in UTUC developmental processes.</p> <p>This review aimed to summarize data available in the literature about underlying molecular mechanisms leading to the expression of miRNAs in AA-UTUC patients with BEN. Strong correlation in AA-UTUC has a distinctive gene alteration pattern, AL-DNA adducts, and a unique tumor protein (TP53) mutational spectrum AAG to TAG (A: T→T: A) transversion in codon 139 (Lys → Stop) of exon 5 activates the p53 tumor suppressor protein. Further, p53 protein is responsible not only for the expression of miRNAs but also acts as a target molecule for miRNAs and plays a crucial function in the AA-UTUC pathogenicity through activation of cyclin-dependent kinase (CyclinD1) and cyclin protein kinase 6(CDK6) to support cell cycle arrest. This study, proposed a molecular mechanism that represented a possible unique relationship between AA intoxication, miRNAs expression, and the progression of UTUC in patients with BEN.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00272023-05-02T00:00:00.000+00:00A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphismhttps://sciendo.com/article/10.2478/bjmg-2022-0026<abstract> <title style='display:none'>ABSTRACT</title> <p>Circadian Clock Protein PERIOD 3 (<italic>PER-3</italic>) is situated on chromosome 1p36.23 and has a polymorphic domain that expresses 4 or 5 copies of the 54-bp tandem repeat sequence. <italic>PER-3</italic> gene polymorphisms play a role in the dysregulation of the immune system. This study intended to investigate the distributions and clinical effectiveness of the <italic>PER-3</italic> gene polymorphism in multiple myeloma (MM) patients. One hundred fifty patients diagnosed between January 2007-2009 and 100 healthy individuals were included in this study. All patients were suitable for autologous stem cell transplantation (ASCT) at first evaluation, and after 4 courses of VCD at least partial remission, ASCT was carried out. Later, LD was used as maintenance. Genotypes of <italic>PER-3</italic> gene of patients and healthy controls were statistically compared before treatment. In addition, these genotypes’ effects on overall and progression free survival (OS and PFS) were investigated. Median PFS in the 5R/5R genotype was found to be significantly longer, albeit low, at 86% (p = 0.046). In the statistical analysis performed between the 4R/4R genotype and others, the PFS of patients with 4R/4R was found to be significantly shorter at 40.4 months (p = 0.026). Patients with the 4R/4R genotype would have a risk of 2.049 times of a shorter PFS (p=0.009). With this first study investigating the effect of a circadian gene in MM, the net effect of <italic>PER-3</italic> gene polymorphism on PFS was revealed, and it will be a guide for future studies.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00262023-05-02T00:00:00.000+00:00Semilobar Holoprosencephaly Caused by a Novel and De Novo Pathogenic Varianthttps://sciendo.com/article/10.2478/bjmg-2022-0017<abstract> <title style='display:none'>ABSTRACT</title> <p>Holoprosencephaly (HPE) is the most common embryonic forebrain developmental anomaly. It involves incomplete or absent division of the prosencephalon into two distinct cerebral hemispheres during the early stages of organogenesis. HPE is etiologically heterogeneous, and its clinical presentation is very variable. We report a case of a 7 month old female infant, diagnosed with non-syndromic semilobar holoprosencephaly, caused by a novel, <italic>de novo</italic> pathogenic variant in <italic>ZIC2</italic> - one of the most commonly mutated genes in non-syndromic HPE coding for the ZIC2 transcription factor. The patient presented with microcephaly, mild facial dysmorphic features, central hypotonia and spasticity on all four extremities. Ultrasound imaging demonstrated the absence of septum pellucidum, semilobar fusion of the hemispheres and mega cisterna magna and brain MRI with confirmed the diagnosis of HPE. Early diagnosis and management are important for the prevention and treatment of complications associated with this condition.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00172023-05-02T00:00:00.000+00:00Adipocyte “Fatty Acid Binding Protein” Gene Polymorphisms ( and ) in Jordanians with Obesity and Type 2 Diabetes Mellitushttps://sciendo.com/article/10.2478/bjmg-2022-0019<abstract> <title style='display:none'>ABSTRACT</title> <sec> <title style='display:none'>Background</title> <p>Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia may result from the interactions of genetic and environmental factors. There are controversial reports concerning the association of polymorphisms (<italic>rs1054135, rs16909196</italic> and <italic>rs16909187</italic>) in the gene of adipocyte fatty acid binding protein (FABP4) with obesity and T2DM. Therefore, we designed this study to determine the association of these polymorphisms with obesity, T2DM, and dyslipidemia among Jordanian subjects.</p> </sec> <sec> <title style='display:none'>Methods</title> <p>The study was approved by the National Center for Diabetes, Endocrinology, and Genetics (NCDEG) Institutional Review Board (IRB). A total of 397 subjects were enrolled in the study and divided into four groups as described in materials and methods section. The fatty acid binding protein 4 (<italic>FABP4)</italic> gene containing (<italic>rs1054135, rs16909196</italic> and <italic>rs16909187</italic>) single nucleotide polymorphisms (SNP) was amplified by polymerase chain reaction (PCR) followed by Sanger DNA sequencing of the PCR product.</p> </sec> <sec> <title style='display:none'>Results</title> <p>None of the three SNPs were associated with T2DM (p &gt; 0.05). The <italic>rs16909187</italic> and <italic>rs16909196</italic> were significantly associated with obesity. The wild type (CC) of <italic>rs16909187</italic> was significantly higher among the overweight and obese group compared with normal weight controls (OD = 2.17, 95% CI = 1.18 - 3.96, p =0.01). The wild type of <italic>rs16909196</italic> (AA) was significantly higher among the overweight and obese group compared to controls, (OD = 2.26, 95% CI = 1.24 - 4.14, p = 0.01). These results may indicate that the wild-type may be a risk factor for obesity.</p> <p>Only the <italic>rs1054135</italic> SNP was significantly associated with increased low density lipoprotein (LDL) levels in the overweight and obese group compared with the controls (p = 0.03).</p> </sec> <sec> <title style='display:none'>Conclusions</title> <p>The wild-type genotypes of <italic>rs16909196</italic> and <italic>rs16909187</italic> may be risk factors for obesity but not T2DM. None of the three SNPs was associated with T2DM.</p> </sec> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00192023-05-02T00:00:00.000+00:00Epidermal Growth Factor Receptor Mutation Status and the Impact on Clinical Outcomes in Patients with Non-Small Cell Lung Cancerhttps://sciendo.com/article/10.2478/bjmg-2022-0015<abstract> <title style='display:none'>ABSTRACT</title> <p>Epidermal growth factor receptor (EGFR) mutation status differs according to ethnicity, gender, smoking history, and histology types. The present study aimed to evaluate EGFR mutation status in patients with non-small cell lung cancer (NSCLC) and further explore its association with clinical characteristics and prognosis in advanced NSCLC patients (Stage IIIB-IV). 238 NSCLC patients were enrolled in this study from October 2016 through December 2019. Patient characteristics and clinical data including age, gender, smoking history, histology types, tumor stage, survival status, and time were collected via electronic medical record system or telephone. 21 somatic mutations which spanned exons 18-21 of EGFR were detected using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method, followed by analysis of links to clinical characteristics, progression-free survival (PFS) and overall survival (OS). 103 patients were detected harboring EGFR mutations among the 238 cases tested (43.3%), and exons 19 and 21 were the highest mutation frequencies, with 20.6% and 19.3% respectively. The EGFR mutation rate was much higher in female versus male (57.4% vs 31.5%, p &lt;0.001), in non-smokers compared to smokers (56.8% vs 25.9%, p &lt;0.001), and in those with adenocarcinoma than other histology types (48.3% vs 3.7%, p &lt;0.001). For patients in advanced stage, median PFS was 11 months in patients harboring EGFR mutations, versus 4 months in patients with wild type EGFR (p &lt;0.001); median OS was 24 versus 12 months (p &lt;0.001). Never smoking (p = 0.042) and adenocarcinoma (p = 0.007) were independent favorable factors for EGFR mutations. Our data strengthen the findings of high prevalence of EGFR mutations in Asian patients with NSCLC. Mutations are prevalent in those patients who are female, adenocarcinoma, and have never smoked. Moreover, advanced EGFR mutation-positive patients have better PFS and OS than those with wild type EGFR.</p> </abstract>ARTICLEtruehttps://sciendo.com/article/10.2478/bjmg-2022-00152023-05-02T00:00:00.000+00:00en-us-1