Balkan Journal of Medical Genetics最新文献

{"title":"<i>Interleukin-1β</i> and <i>Tumor Necrosis Factor-α</i> Gene Polymorphisms in Systemic Sclerosis.","authors":"M A Hakami, B S Alotaibi, S S Alkhalil, S Das, N Nasreen, M A Jeraiby, A Jawed, M Lohani, S A Dar","doi":"10.2478/bjmg-2024-0017","DOIUrl":"10.2478/bjmg-2024-0017","url":null,"abstract":"<p><p>The complex cytokine network plays an important role in disease susceptibility and development, therefore single-nucleotide polymorphisms (SNPs) in or near cytokine genes may be relevant to development of systemic sclerosis (SSc). We in this study investigated 22 SNPs in 13 cytokine genes of SSc patients, and their association with disease susceptibility. Twenty-three clinically diagnosed SSc patients were enrolled for this purpose along with 80 healthy volunteers for comparisons. Aseptically collected 2ml of peripheral venous blood from each subject was processed for DNA extraction. Cytokine genotyping was carried out using the extracted genomic DNA by PCR employing sequence-specific primers and data was analyzed for any association with SSc susceptibility. Variations in allele, genotype, or haplotype distribution between patients and healthy volunteers were observed for the following SNPs: <i>IL-1β</i> -511 C/T (rs16944) and +3962 T/C (rs1143634); <i>IL-4Rα</i> +1902 G/A (rs1801275); <i>IL-12</i> -1188 C/A (rs3212227); <i>TGF-β1</i> codon 25 G/C (rs1800471); <i>TNF-α</i>-308 G/A (rs1800629) and -238 G/A (rs361525); <i>IL-4</i> -1098 T/G (rs2243248) and -590 T/C (rs2243250); <i>IL-6</i> -174 G/C (rs1800795) and nt565 G/A (rs1800797); and <i>IL-10</i> -1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872). However, only the SNPs in <i>IL-1β</i> -511 and +3962, and <i>TNF-α</i> -308 and -238 were found to be significantly associated with SSc susceptibility. Our findings suggest that <i>IL-1β</i> and <i>TNF-α</i> gene SNPs may play a role in development of SSc, although large observational and experimental studies are needed to substantiate these findings.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"59-68"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607306","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}

{"title":"Delineation of Partial Chromosomal Abnormalities in Early Pregnancy Losses.","authors":"Gj Bozhinovski, M Terzikj, K Kubelka-Sabit, D Plaseska-Karanfilska","doi":"10.2478/bjmg-2024-0014","DOIUrl":"10.2478/bjmg-2024-0014","url":null,"abstract":"<p><p>Pregnancy loss (PL), particularly early pregnancy loss (EPL), is a prevalent reproductive complication, with approximately 15% of confirmed pregnancies affected. Chromosomal abnormalities are implicated in more than half of EPLs, with trisomies being the most prevalent. Partial abnormalities, including segmental deletions, duplications, and unbalanced translocations, are detected in up to 10% of EPL cases. This study focuses on the precise characterization of partial chromosomal abnormalities, previously identified by Quantitative fluorescent polymerase chain reaction (QF-PCR) and multiplex ligation probe amplification (MLPA) analyses. By employing an array comparative genomic hybridization (aCGH), we analyzed 20 EPL samples, identifying 32 partial chromosomal abnormalities, including 18 deletions and 14 duplications, with an average size of 33.2 Mb. Notably, two abnormalities previously undetected by QF-PCR and MLPA were revealed (deletions in 7q36, and 1p36.32p36.31regions), emphasizing the necessity of high-resolution genomic tools. Chromosomes 1, 18, and 13 emerged as frequently involved, aligning with previous associations with recurrent pregnancy loss. Recurrent abnormalities were identified in six chromosomal regions, with chromosome 1p36.33-p36.32 exhibiting the highest frequency. Gene Ontology (GO) enrichment analysis of recurrent regions highlighted disruptions in critical biological processes, including molecular binding, enzymatic activity, and cellular development. Many genes in these regions are linked to multisystem syndromes, suggesting their involvement in early embryonic development and pregnancy viability. Our findings underscore the complexity of EPL's genetic landscape, demonstrating that large CNVs, may disrupt multiple genes critical for development. Although, subtelo-meric MLPA reliably detects telomeric partial chromosomal abnormalities in EPLs, aCGH is essential for detection and precise characterization of all CNVs, thus enhancing diagnostic and counseling strategies in affected couples.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"23-32"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607314","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}

{"title":"Investigation of TLR4 Polymorphism in Children with Vesicoureteral Reflux and Renal Scarring.","authors":"N M Sav, R Eroz, Duran N Kalay, O Kilicaslan, Karaca S Erisen","doi":"10.2478/bjmg-2024-0013","DOIUrl":"10.2478/bjmg-2024-0013","url":null,"abstract":"<p><p>Vesicoureteral reflux (VUR) is an important factor in the etiology of recurrent urinary tract infections (UTIs). Permanent kidney damage may develop in children with high-grade VUR in the long term. This damage may progress with the development of scar tissue in some patients. The <i>TLR4</i> gene is an important resistance mechanism, especially against UTIs. <i>TL</i>R4 gene polymorphism is associated with recurrent UTIs and kidney scar development in the long term. This study aimed to examine the relationship between scar development and <i>TLR4</i> gene polymorphism in children with VUR. This cross-sectional study included 49 patients with recurrent UTIs and primary vesicoureteral reflux. Patients were divided into two groups (26 patients with the scar, and 23 patients without scar) according to the presence of scar tissue. <i>TLR4</i> gene polymorphisms of the patients were evaluated by Next Generation Sequencing. The <i>TLR4</i> gene polymorphism was significantly higher in the compound heterozygous group with scarring than in the group without scarring (p=0.03). Gene polymorphisms, c.958T>C, c.942A>G, c.776A>G, c.1076C>T, c.896A<G, c.1196C>T, c.1078C>T were presented more commonly in the group with scarring. Moreover, gene polymorphisms c.942A>G and c.776A>G were defined for the first time in this study among patients with scar tissue. The higher incidence of some <i>TLR4</i> gene polymorphisms in patients with scarring suggested that these variations might cause permanent kidney damage. In addition to genetic predisposition, environmental factors such as untreated UTIs might also contribute to scar formation.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"41-47"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607318","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}

{"title":"<i>CREBBP</i> is a Major Prognostic Biomarker for Relapse in Childhood B-cell Acute Lymphoblastic Leukemia: A National Study of Unselected Cohort.","authors":"E Krstevska Bozhinovikj, N Matevska-Geshkovska, M Staninova Stojovska, E Gjorgievska, A Jovanovska, S Kocheva, A Dimovski","doi":"10.2478/bjmg-2024-0020","DOIUrl":"10.2478/bjmg-2024-0020","url":null,"abstract":"<p><p>Although the identification of disease subtypes conveying prognostic significance along with minimal residual disease (MRD) assessment represent cornerstones for stratification in childhood acute lymphoblastic leukemia (ALL), approximately half of the relapses occur in patients from standard-risk groups. Identification of the drivers of treatment failure is crucial for detection of high-risk clones at diagnosis. We evaluated clinical variables and the most common genetic alterations in an unselected cohort of 55 patients with B-ALL treated according to the ALL-IC-BFM 2002 protocol, with a median follow-up of 46 months. Matched diagnosis-relapse samples underwent screening for additional alterations using whole-exome sequencing. Mutations in the <i>CREBBP</i> gene were found in 80% (4/5) of the patients with relapse, either present from the disease onset or acquired at relapse, while none of the examined patients in remission presented alterations in this gene. Deletions in <i>TP53</i> and <i>EBF1</i> (present in 2/5 and 1/5 of the patients with relapse, respectively) were infrequent or absent in the patients in remission, respectively. Screening for alterations in the <i>CREBBP</i> gene at diagnosis and/or at multiple time-points during chemotherapy could be incorporated into treatment protocols, as it may contribute to the identification of significant number of patients with predefined or acquired chemoresistant clones.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"5-12"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607301","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}

{"title":"In Vitro Analysis of AKR1D1 Interactions with Clopidogrel: Effects on Enzyme Activity and Gene Expression.","authors":"K Shutevska, Panovska T Kadifkova, Z Zhivikj, Nestorovska A Kapedanovska","doi":"10.2478/bjmg-2024-0012","DOIUrl":"10.2478/bjmg-2024-0012","url":null,"abstract":"<p><p>Clopidogrel, a P2Y12 receptor antagonist, is widely used to prevent cardiovascular events, but significant variability in its efficacy persists among patients. AKR1D1, involved in bile acid synthesis and regulation of CYP enzymes, may contribute to this variability. This study aims to investigate whether clopidogrel and its inactive metabolite, 2-oxoclopidogrel, interact with AKR1D1 at the enzymatic or transcriptional level. Enzymatic activity assays demonstrated that neither clopidogrel nor 2-oxoclopidogrel acts as a substrate or inhibitor of AKR1D1. Expression studies in HepG2 cells further revealed no significant changes in <i>AKR1D1</i> mRNA levels following treatment with these compounds. These findings indicate that clopidogrel does not directly influence AKR1D1's metabolic functions, including bile acid synthesis, steroid hormone clearance, or the production of 5β-reduced steroids, which regulate CYP enzyme expression. From a physiological perspective, the absence of interaction minimizes the risk of adverse effects on CYP-mediated drug metabolism, nutrient absorption, lipid digestion, and the absorption of lipophilic drugs. Future research should explore AKR1D1's broader substrate specificity, particularly focusing on non-steroidal compounds, and investigate the clinical implications of AKR1D1 polymorphisms in clopidogrel-treated patients to enhance personalized therapeutic strategies.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"69-75"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607315","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}

{"title":"Value of Optical Genome Mapping (OGM) for Diagnostics of Rare Diseases: A Family Case Report.","authors":"A Kovanda, O Miljanović, L Lovrečić, A Maver, A Hodžić, B Peterlin","doi":"10.2478/bjmg-2024-0021","DOIUrl":"10.2478/bjmg-2024-0021","url":null,"abstract":"<p><p>Optical genome mapping (OGM) is a novel method enabling the detection of structural genomic variants. The method is based on the laser image acquisition of single, labeled, high-molecular-weight DNA molecules and can detect structural genomic variants such as translocations, inversions, insertions, deletions, duplications, and complex structural rearrangements. We aim to present our experience with OGM at the Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Slovenia. Since its introduction in 2021, we have used OGM for the testing of facioscapulohumeral muscular dystrophy 1, characterization and resolution of variants identified by other technologies such as microarrays, exome and genome next-generation sequencing, karyotyping, as well as testing of rare disease patients in whom no genetic cause could be identified using these methods. We present an example family case of two previously undiagnosed male siblings with an overlapping clinical presentation of thrombocytopenia, obesity, and presacral teratoma. After karyotyping, microarray analysis and next-generation sequencing, by using OGM, a maternally inherited cryptic translocation t(X;18)(q27.1;q12.2) was identified in both brothers. Despite an extended segregation analysis, based on strictly applied ACMG criteria and ClinGen guidelines, the identified translocation remains a variant of unknown significance. Despite the remaining limitations of OGM, which will hopefully be resolved by improvements in databases of known benign SV variation and the establishment of official guidelines on the clinical interpretation of OGM variants, our work highlights the complexity of the diagnostic journey, including this novel method, in rare disease cases.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"87-93"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607322","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}

{"title":"Association of <i>CYP2C19*2</i> c.681G>A (rs4244285) Loss-of-function Allele with Cardiovascular Disease Risk in the Kosovo Population.","authors":"N Elshani, K Ukella, Stojovska M Staninova, Z Naumovska, M Kurshumliu, D Gorani, Nestorovska A Kapedanovska","doi":"10.2478/bjmg-2024-0015","DOIUrl":"10.2478/bjmg-2024-0015","url":null,"abstract":"<p><p>The <i>CYP2C19*2 c.681G>A (rs4244285)</i> loss-of-function (<i>LOF</i>) allele has been associated with reduced clopidogrel efficacy and increased risk of major adverse cardiovascular events (MACE). PGx-guided treatment, despite the recommendations, is not fully implemented in routine clinical practice. The primary aim of this hybrid retrospective-prospective study was to determine whether identifying <i>CYP2C19</i> LOF patients may benefit the antiplatelet drug prescribing decisions made in Kosovo. The study cohort consisted of clopidogrel treated patients presenting at the University Clinical Center in the period from December 2023 to May 2024. To evaluate the correlation between <i>CYP2C19</i> LOF and the treatment outcome in a follow-up period of 2 years, we first assessed the <i>CYP2C19*2</i> genotype using the Taq Man Real Time PCR method. Among 150 patients, 58 (19.33%) were identified as carriers <i>CYP2C19*2 LOF</i> allele. The observed allele distribution was significantly different when compared with the one reported for a healthy Kosovar population (13.03%). <i>CYP2C19*2</i> LOF carriers exhibited a 1.6-fold higher probability of developing cardiovascular disease compared to non-carriers, based on allelic and codominant model of statistical analysis (OR=1.60; 95% CI=1.08-2.37; p=0.018 and OR=1.64; 95% CI=1.04-2.57; p=0.031, respectively). The median observation time of follow up was not reached until this analysis was conducted. Our data supports the potential association of the <i>CYP2C19*2 LOF</i> allele with an increased risk for CVD in the population of Kosovo. Our data add to the evidence advising careful consideration of <i>CYP2C19</i> genetic diversity when recommending PGx-guided clopidogrel therapy, particularly in populations, such the Kosovar, where genetic determinants are not yet fully elucidated.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"77-85"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607310","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}

{"title":"Chromosomal Microarray in Children Born Small for Gestational Age - Single Center Experience.","authors":"D Perović, P Barzegar, T Damnjanović, B Jekić, M Grk, M Dušanović Pjević, D Cvetković, A Đuranović Uklein, N Stojanovski, M Rašić, I Novaković, B Elhayani, N Maksimović","doi":"10.2478/bjmg-2024-0018","DOIUrl":"10.2478/bjmg-2024-0018","url":null,"abstract":"<p><p>The association between small for gestational age birth and chromosomal abnormalities identified through karyotyping is well-established. Notably, advancements in cytogenetic techniques have shifted from routine karyotyping to the recommended use of microarray technology. This transition allows higher resolution and the detection of sub-microscopic copy number variants (CNVs). Our study included 49 patients born small for gestational age, 27 males and 22 females. Clinical data were gathered from reports by clinical genetic specialists, and a questionnaire was included in the referral list to our laboratory. All participants were of pediatric age, ranging from neonatal to 12 years old. Chromosomal microarray testing was conducted by the Agilent SurePrint G3 Human CGH Microarray 8×60K. The application of molecular karyotyping yielded clinically significant results in 16 cases (32.65%), which included 13 deletions and 6 duplications. Three patients presented with two clinically significant CNVs (csCNVs). In ten cases, we identified recurrent microdeletion or microduplication syndromes well-documented in the literature: Williams syndrome as the most commonly identified (three patients), and others like Koolen de Vries, Prader-Willi, Miller-Dieker, Dryer, DiGeorge syndrome, 7q11.23 microduplication, 16p13.11 microdeletion, and 1q21.1 microdeletion syndrome. Six patients had rare non-recurrent pathological CNVs. There was no statistically significant difference between patients with csCNVs and those without regarding the presence of intellectual disabilities, central nervous system, cardiac or skeletal malformations. Chromosomal microarray proves to be a useful diagnostic tool in the etiology diagnosis of children born small for gestational age.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"13-21"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607311","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}

{"title":"Phenotypic Variability of Cowden Syndrome Within a Single Family: Impact on Diagnosis, Management and Genetic Counselling.","authors":"N Ilic, N Mitrovic, R Radeta, S Krasić, V Vukomanović, G Samardzija, M Vasic, A Vlahovic, A Sarajlija","doi":"10.2478/bjmg-2024-0016","DOIUrl":"10.2478/bjmg-2024-0016","url":null,"abstract":"<p><p>Cowden syndrome (CS) represents a rare autosomal dominant disorder caused by mutations in the <i>PTEN</i> gene located on chromosome 10q23.3. This entity belongs to the PTEN hamartoma tumor syndrome (PHTS) spectrum. The <i>PTEN</i> gene encodes a tumor suppressor protein crucial for regulating cell growth, survival, and apoptosis. Pathogenic mutations in <i>PTEN</i> result in dysregulated cell proliferation, manifesting clinically as benign and malignant growths across various tissues. CS is characterized by a predisposition to multiple hamartomas and an elevated risk of cancers, most notably in the skin, soft tissues, thyroid, breast, and gastrointestinal tract. In pediatric patients, macrocephaly is frequently the earliest feature, often accompanied by developmental delays and neurological deficits. This case series details the clinical evolution and multidisciplinary management of two siblings with CS and normal psychomotor development. Genetic testing identified a familial <i>PTEN</i> mutation, with multiple affected relatives, including the siblings' father, paternal aunt and paternal grandfather, each displaying distinct phenotype. This familial clustering highlights the autosomal dominant inheritance of CS and points out the critical importance of early genetic testing, vigilant surveillance, and tailored counselling for at-risk relatives. Phenotypic variability observed between members of the same family points out the difficulties in predicting transgenerational outcomes and complicates genetic counselling.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"95-100"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607321","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}

{"title":"Next-Generation Sequencing Infertility Panel in Turkey: First Results.","authors":"E Ikbal Atli, S Yalcintepe, E Atli, S Demir, H Gurkan","doi":"10.2478/bjmg-2024-0019","DOIUrl":"10.2478/bjmg-2024-0019","url":null,"abstract":"<p><strong>Background: </strong>Male infertility is a complex pathophysiological disorder. At least 2000 genes are implicated in the etiology of male infertility, making it a very complex genetic condition. In cases of male infertility, genetic testing using next-generation sequencing (NGS) technology may be useful for diagnosis. Thus, the purpose of this investigation was to apply the diagnostic offer for genetic variant identification using an NGS panel.</p><p><strong>Methods: </strong>We developed an NGS gene panel that we used in 85 infertile male patients. The panel consisted of 132 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia etc.</p><p><strong>Results: </strong>A total of 85 patients (85 males) between 21 year and 45 years old were included in the study group. NGS analysis had been applied in all the primary infertility cases. As a result of NGS analysis, 58 clinical variants in 28 genes were detected in 41 patients (%48.23- 41/85).</p><p><strong>Conclusion: </strong>Consequently, pre-diagnostic genes included in a custom-made NGS panel test can enhance genetic diagnostic testing and have an impact on the clinical management of male infertility.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":"27 2","pages":"49-57"},"PeriodicalIF":0.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607319","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}