Balkan Journal of Medical Genetics最新文献

{"title":"A New Clock is Running for Multiple Myeloma: Circadian Clock Protein-Period 3 (PER-3) Polymorphism.","authors":"I Serin,&nbsp;S Pehlivan,&nbsp;I Demir,&nbsp;Y Oyacı,&nbsp;M Pehlivan","doi":"10.2478/bjmg-2022-0026","DOIUrl":"https://doi.org/10.2478/bjmg-2022-0026","url":null,"abstract":"<p><p>Circadian Clock Protein PERIOD 3 (<i>PER-3</i>) is situated on chromosome 1p36.23 and has a polymorphic domain that expresses 4 or 5 copies of the 54-bp tandem repeat sequence. <i>PER-3</i> gene polymorphisms play a role in the dysregulation of the immune system. This study intended to investigate the distributions and clinical effectiveness of the <i>PER-3</i> 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 <i>PER-3</i> 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 <i>PER-3</i> gene polymorphism on PFS was revealed, and it will be a guide for future studies.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/dc/bjmg-25-2-bjmg-2022-0026.PMC10230830.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568032","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":"Congenital Hepatic Fibrosis as an Early Sign of Presentation of ADPKD.","authors":"L Sila,&nbsp;V Velmishi,&nbsp;B Saraci,&nbsp;E Dervishi,&nbsp;S Sila,&nbsp;D Shtiza,&nbsp;P Cullufi","doi":"10.2478/bjmg-2022-0024","DOIUrl":"https://doi.org/10.2478/bjmg-2022-0024","url":null,"abstract":"<p><p>Autosomal dominant polycystic kidney disease (ADKPD) is the most frequent type of polycystic kidney disease. It is inherited through family members, with an incidence of approximately 1:400 to1:1000.Typically, individuals with ADKPD are identified between their fourth and fifth decade of life. ADKPD occurs as a results of mutation in one of the two genes, <i>PDK1</i> and <i>PDK2</i>.Patients with PKD1 experience renal failure at an earlier onset than those with PKD2. We report on a 2 year-old-boy with hepatosplenomegaly and signs of portal hypertension. Both kidneys appeared normal until the age of 8, when multiple cysts developed, this being typical of ADKPD. Suspecting ADKPD, we performed whole exome sequencing, thereby confirming a mutation of c.6730 673del p.(Ser 2244Hisfs*17). The investigations of all family members found other individuals affected by ADKPD.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/ba/bjmg-25-2-bjmg-2022-0024.PMC10230838.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940525","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":"KDM3A, a Novel Blood-Based Biomarker in Colorectal Carcinogenesis.","authors":"D Polat,&nbsp;E Onur,&nbsp;N Yılmaz,&nbsp;M Sökücü,&nbsp;O F Gerçeker","doi":"10.2478/bjmg-2022-0021","DOIUrl":"https://doi.org/10.2478/bjmg-2022-0021","url":null,"abstract":"<p><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 <i>KDM3A</i> gene could be used as a predictor of CRC. The expression levels of <i>HIF-1α, KDM3A</i>, 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. <i>HIF-1α</i> and <i>KDM3A</i> expression levels were significantly higher in the CRC group, compared to the controls. <i>Slug</i> and <i>ZEB-1</i> 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 <i>KDM3A</i> expression levels in ROC analysis. This data support that <i>KDM3A</i> could be a novel supplementary biomarker in diagnosis of CRC, which could be noninvasively detected in circulation.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/83/bjmg-25-2-bjmg-2022-0021.PMC10230839.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940526","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":"Rare and New Mutations of B-Globin in Azari Population of Iran, a Considerable Diversity.","authors":"F H Abbasali,&nbsp;K Sh Mahmoud,&nbsp;N Hengameh,&nbsp;D H Mina,&nbsp;D Setare,&nbsp;D M Hale,&nbsp;D M Sima","doi":"10.2478/bjmg-2022-0016","DOIUrl":"https://doi.org/10.2478/bjmg-2022-0016","url":null,"abstract":"<p><strong>Background: </strong>Thalassemia, as the most common single-gene genetic disorder, is related to a defect in the synthesis of one or more hemoglobin chains. More than 200 mutations have been identified in the β-globin gene. Globally, every susceptible racial group has its own specific spectrum of the common mutations that are well-known to a particular geographic region. On the other hand, varying numbers of diverse rare mutations may occur.</p><p><strong>Materials and methods: </strong>The subjects of the study included 2113 heterozygote or homozygote β-thalassemia cases selected among couples who participated in the Iranian national thalassemia screening program from January 2011 to November 2019. Molecular characterization of the β-thalassemia mutation was initially carried out by the amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) technique for common mutations, followed by sequencing, Gap PCR, and Multiple ligation-dependent probe amplification (MLPA) methods - in cases not detected by the ARMS-PCR.</p><p><strong>Results: </strong>The existence of 39 rare and new point mutations and 4 large deletions were described in our cohort. Sicilian (-13,337bp) deletion, CD36/37 (-T), and CD15 TGG>TGA were encountered more often than the others in a decreasing order, in terms of frequency. The least frequent mutations/deletions were deletion from HBD exon 1 to HBB promoter, 619 bp deletion, Deletion from up HBBP1-Exon3 HBBP1 and up HBB-0.5Kb down HBB, CAP+8 C>A, CD37 (G>A), CD6 (-A), IVSI-2 (T>C), IVSII-705 T>G, and IVSII-772 (G>A). Each occurred once. Five mutations/variants were also determined which have not been reported previously in Iran.</p><p><strong>Conclusion: </strong>According to the findings of the study, the Northwestern Iranian population displayed a wide variety of thalassemia allelic distributions. Identification of rare and new mutations in the β-thalassemia in the national population is beneficial for screening programs, genetic counseling, and prenatal diagnosis.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/e4/bjmg-25-2-bjmg-2022-0016.PMC10230832.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9559673","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":"Semilobar Holoprosencephaly Caused by a Novel and De Novo <i>ZIC2</i> Pathogenic Variant.","authors":"D Nonkulovski,&nbsp;A Sofijanova,&nbsp;T Spasovska,&nbsp;Milanovski Gorjan,&nbsp;Lj Muaremoska-Kanzoska,&nbsp;T Arsov","doi":"10.2478/bjmg-2022-0017","DOIUrl":"https://doi.org/10.2478/bjmg-2022-0017","url":null,"abstract":"<p><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, <i>de novo</i> pathogenic variant in <i>ZIC2</i> - 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>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/23/bjmg-25-2-bjmg-2022-0017.PMC10230831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568027","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":"Molecular 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 Literature.","authors":"D Bašić,&nbsp;I Ignjatović,&nbsp;Lj Janković Veličković,&nbsp;A Veljković","doi":"10.2478/bjmg-2022-0027","DOIUrl":"https://doi.org/10.2478/bjmg-2022-0027","url":null,"abstract":"<p><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. 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>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/86/bjmg-25-2-bjmg-2022-0027.PMC10230835.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9559672","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":"Epidermal Growth Factor Receptor Mutation Status and the Impact on Clinical Outcomes in Patients with Non-Small Cell Lung Cancer.","authors":"H M Huang,&nbsp;Y Wei,&nbsp;J J Wang,&nbsp;F Y Ran,&nbsp;Y Wen,&nbsp;Q H Chen,&nbsp;B F Zhang","doi":"10.2478/bjmg-2022-0015","DOIUrl":"https://doi.org/10.2478/bjmg-2022-0015","url":null,"abstract":"<p><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 <0.001), in non-smokers compared to smokers (56.8% vs 25.9%, p <0.001), and in those with adenocarcinoma than other histology types (48.3% vs 3.7%, p <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 <0.001); median OS was 24 versus 12 months (p <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>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/1a/bjmg-25-2-bjmg-2022-0015.PMC10230834.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568028","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":"Double Isochromosome X, a Rare Cytogenetic Variant of Turner Syndrome: A Case Report and a Review of the Literature.","authors":"K Zerrouki,&nbsp;Errahhali M Elidrissi,&nbsp;Errahhali M Elidrissi,&nbsp;A Babakhouya,&nbsp;M Tajir","doi":"10.2478/bjmg-2022-0011","DOIUrl":"10.2478/bjmg-2022-0011","url":null,"abstract":"<p><p>Turner Syndrome (TS) is a genetic disorder caused by total or partial loss of an X chromosome. The isochromosome X (i(X)) is a known variant of TS, however, double i(X) is a very rare variant, reported very few times in the literature. We report on a rare case of TS with double i(X). This is an 11-year-old female patient , addressed to the medical genetics consultation for short stature and facial features suggestive of TS. We performed a constitutional postnatal karyotype from a peripheral blood sample, with lymphocyte culture, and an R band analysis, performed on 70 metaphases. Metaphases analysis in our patient identified the presence of three cell populations: 45,X[22]/46,X,i(X)(q10)[30]/47,X,i(X)(q10),i(X)(q10) [18]. The first has total chromosome X monosomy, the second with a normal X chromosome and one isochromosome of the long arm of the other X chromosome and the third with a normal X chromosome and two isochromosomes of the long arm of the X chromosome. A control cell culture was performed from a second blood sample of the patient and confirmed the abnormality. This paper will discuss this case in comparison with other rare cases described, as well as the formation of the double isochromosome, based on the literature.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/ce/bjmg-25-101.PMC9985355.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626371","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":"Single Nucleotide Polymorphisms in IL-1A RS1800587, IL-1B RS1143634 and Vitamin D Receptor Rs731236 in Stage III Grade B/C Periodontitis.","authors":"Özener H Özturk, Aslan B Tacal, B F Eken, Ö B Agrali, H S Yildrim, E Ç Altunok, K Ulucan, L Kuru","doi":"10.2478/bjmg-2022-0005","DOIUrl":"10.2478/bjmg-2022-0005","url":null,"abstract":"<p><p>The purpose of the study is to determine the prevalence of interleukin (IL)-1A (rs1800587), <i>IL-1B</i> (rs1143634) and vitamin D receptor (<i>VDR</i>) (<i>TaqI</i>, rs731236) gene polymorphisms in the Turkish population and their association with Stage III Grade B/C periodontitis. Systemically and periodontally healthy individuals (N = 100) and Stage III Grade B/C periodontitis patients (N=100) based on clinical and radiographic examination were included in this research. Clinical attachment level, probing depth, bleeding on probing, plaque and gingival indices of the subjects were measured. Genotyping of <i>IL-1A</i> (rs1800587), <i>IL-1B</i> (rs1143634) and <i>VDR</i> (rs731236) polymorphisms was conducted by Real Time PCR. Allelic and genotypic distributions of <i>IL-1A</i> (rs1800587) gene polymorphism were not associated with periodontitis (p>0.05). In <i>IL-1B</i> (rs1143634) gene polymorphism, the C allele was detected more frequently in healthy individuals compared with the periodontitis patients (p=0.045). CC genotype and C allele in <i>VDR</i> (rs731236) gene polymorphism was higher in periodontitis patients (p=0.031, p=0.034, respectively). In comparison with Grade B periodontitis patients and healthy subjects, CC genotype and C allele were observed more frequently in the Grade B periodontitis in terms of alleles (C/T) and genotypes for <i>VDR</i> (rs731236) polymorphism (p=0.024, p=0.008, respectively). This study presents that the <i>VDR</i> (rs731236) polymorphism are associated with enhanced susceptibility to Stage III periodontitis in the Turkish population. Furthermore, <i>VDR</i> (rs731236) polymorphism may be used as an identification criteria to discriminate Grade B and Grade C in Stage III periodontitis.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/20/bjmg-25-051.PMC9985357.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9408558","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>de Novo TINF2</i> C.845G>A: Pathogenic Variant in Patient with Dyskeratosis Congenita.","authors":"S A Kocheva,&nbsp;M Gjorgjievska,&nbsp;K Martinova,&nbsp;Z Antevska-Trajkova,&nbsp;A Jovanovska,&nbsp;D Plaseska-Karanfilska","doi":"10.2478/bjmg-2021-0027","DOIUrl":"https://doi.org/10.2478/bjmg-2021-0027","url":null,"abstract":"<p><p>Dyskeratosis congenita (DC) is a clinically and genetically heterogeneous, multisystem inherited syndrome with a very high risk for bone marrow failure (BMF) and cancer predisposition. The classical clinical form of DC is characterized by abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. Bone marrow failure is considered to be an important and major complication of DC and the leading cause of death which develops in around 85% of cases. A number of genes involved in telomere maintenance are associated with DC, such as genes that encode the components of the telomerase complex (<i>TERT</i>, <i>DKC1</i>, <i>TERC</i>, <i>NOP</i>10, and <i>NHP</i>2), T-loop assembly protein (<i>RTEL1</i>), telomere capping (<i>CTC1</i>), telomere shelterin complex (<i>TINF2</i>), and telomerase trafficking protein (<i>TCAB1</i>). Mutations in <i>TINF2</i> have been reported in 11-20% of all patients with DC and have been associated with bone marrow failure. Here we report on a 19-month old boy with very early presentation of bone marrow failure as a first clinical manifestation of DC. Upon first admission, the patient presented with thrombocytopenia and macrocytic anemia. Soon after, his blood counts deteriorated with the development of pancytopenia and aplastic anemia. Four months later, he developed nail dystrophy and skin hyperpigmentation. A <i>de novo</i> heterozygous pathogenic variant c.845G>A, p.(Arg282His) was located in exon 6 of <i>TINF2</i> gene and was identified via clinical exome sequencing. The findings confirmed the diagnosis of DC. This is the first case with DC due to <i>TINF2</i> pathogenic variant reported in North Macedonia.</p>","PeriodicalId":55403,"journal":{"name":"Balkan Journal of Medical Genetics","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/fa/bjmg-24-089.PMC9524180.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33518376","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}