Balkan Journal of Medical Genetics最新文献

Multiple second heart field (SHF) transcription factors are involved in cardiac development. In this article we evaluate the relationship between SHF transcription factor polymorphisms and congenital heart disease (CHD). Ten polymorphisms were used for genotyping, and three of these were used for the luciferase assay. The risk of CHD was increased 4.31 times and 1.54 times in the C allele of GATA5: rs6061243 G>C and G allele of TBX20: rs336283 A>G, respectively. The minor alleles of SMYD1: rs1542088 T>G, MEF2C: rs80043958 A>G and GATA5: rs6587239 T>C increased the risk of the simple types of CHD. The minor alleles of GATA5: rs41305803 G>A and MEF2C: rs304154 A>G increased the risk of tetralogy of Fallot (TOF). The minor alleles of TBX20: rs336284 A>G and SMYD1: rs88387557 T>G only increased the risk of a single ventricle (SV). Luciferase assays revealed that the minor alleles of rs304154 and rs336284 decreased the transcriptional levels of MEF2C and TBX20, respectively (p<0.01). When combined with HLTF, the G promoter showed a higher expression level than the A promoter in rs80043958 (p<0.01). Our findings suggest that minor alleles of SNPs in the exonic and promoter regions of transcription factors in the SHF can increase the risks of sporadic CHD.

Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome caused by mutations on the NF1 gene, which is located at chromosome 17q11.2. Although an autosomal dominant inheritance pattern is well-established, about half of new cases are the result of de novo NF1 mutations. Neurofibromatosis type 1 has an incidence rate of 1/2600-3000 individuals, making it a major public health problem. The product of the NF1 gene, the neurofibromin protein, is known to play a critical role in cellular differentiation and in tumor suppression. Due to widespread expression of neurofibromin in numerous tissues, particularly in cutaneous and nervous systems, NF1 mutations cause a wide variety of clinical symptoms, including cutaneous and ocular lesions such as café au lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, iris Lisch nodules, choroidal freckling and internal tumors. In this article, we report the cases of two siblings with NF1, a 21-year-old male and his 24-year-old sister, who have the same c.5392C>T mutation on the NF1 gene (p.Gln1798 Ter). Café au lait macules and freckling were the prominent clinical features in both siblings. However, a plexiform neurofibroma was also observed on the left arm of the sister, which is known to carry potential risk for malignant transformation. Although the mutation was previously described once, to the best of our knowledge, no case report has been published since then.

Chromosome 17q12 microdeletion syndrome is a contiguous gene deletion syndrome caused by an 1-2 Mb loss, characterized by multicystic dysplastic kidneys or other urinary system anomalies starting in utero, including autism or maturity-onset diabetes of the young in its postnatal phenotype. Here, we report on three cases (two prenatal and one postnatal) with distinct and novel clinical presentations as compared with a large number of reviewed patients, thus emphasizing the phenotypic variability of this syndrome and the consequent difficulties in genetic counselling. Prenatal hyperechogenic multicystic kidneys, as well as other urinary tract anomalies, should be considered a marker, therefore indicating the necessity of comprehensive genetic testing, and autism should also be acknowledged as a possible clinical presentation, postnatally.

Developmental delay (DD) is a condition wherein developmental milestones and learning skills do not occur at the expected age range for patients under 5 years of age. Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and cause-effect relationships. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Array-based comparative genomic hybridization aCGH) can detect copy number variations (CNVs) on the whole genome at higher resolution than conventional cytogenetic methods. The diagnostic yield of aCGH was 15.0-20.0% in DD/ID cases. The aim of this study was to discuss the clinical findings and aCGH analysis results of isolated and syndromic DD/ID cases in the context of genotype-phenotype correlation. The study included 139 cases (77 females, 62 males). Data analysis revealed 38 different CNVs in 35 cases. In this study, 19 cases with pathogenic CNVs (13.6%) and five cases with likely pathogenic CNVs (3.5%) were found in a total of 139 cases diagnosed with DD/ID. When all pathogenic and likely pathogenic cases were evaluated, the diagnosis rate was 17.1%. The use of aCGH analysis as a first-tier test in DD/ID cases contributes significantly to the diagnosis rates and enables the detection of rare microdeletion/microduplication syndromes. The clear determination of genetic etiology contributes to the literature in terms of genotype-phenotype correlation.

The goal of the study was to retrospectively evaluate a cohort of children and adults with mitochondrial diseases (MDs) in a single-center experience. Neurological clinical examination, brain magnetic resonance imaging (MRI) and spectroscopy, muscle biopsy, metabolic and molecular-genetic analysis were evaluated in 26 children and 36 adult patients with MD in Slovenia from 2004 to 2018. Nijmegen MD criteria (MDC) were applied to all patients and the need for a muscle biopsy was estimated. Exome-sequencing was used in half of the patients. Twenty children (77.0%) and 12 adults (35.0%) scored a total of ≥8 on MDC, a result that is compatible with the diagnosis of definite MD. Yield of exome-sequencing was 7/22 (31.0%), but the method was not applied systematically in all patients from the beginning of diagnostics. Brain MRI morphological changes, which can be an imaging clue for the diagnosis of MD, were found in 17/24 children (71.0%). In 7/26 (29.0%) children, and in 20/30 (67.0%) adults, abnormal mitochondria were found on electron microscopy (EM) and ragged-red fibers were found in 16/30 (53.0%) adults. Respiratory chain enzymes (RCEs) and/or pyruvate dehydrogenase complex (PDHc) activities were abnormal in all the children and six adult cases. First, our data revealed that MDC was useful in the clinical diagnosis of MD, and second, until the use of NGS methods, extensive, laborious and invasive diagnostic procedures were performed to reach a final diagnosis. In patients with suspected MD, there is a need to prioritize molecular diagnosis with the more modern next-generation sequencing (NGS) method.

Importunate high-risk HPV (HR-HPV) infection is the most common trigger for the cervical carcinogenesis process. In this respect, the presence of cancer can be imputed to telomere lengthening or shortening. This paper explores the possible correlation between relative telomere length and viral load in two groups of women, namely: those with high-risk HPV infection and those who do not have this infection. Thus, samples comprising of 50 women in each group were evaluated for this research. The Amplisens HPV HCR screen-titre-FRT PCR kite was employed for quantitative analysis. Relative telomere length was quantified by real-time PCR. In each of the two HPV load groups, there was no correlation between age and telomere length. Telomere shortening was found in the cervical cell samples of women with high HPV loads, compared with women in the control group. Telomere shortening is associated with elevated HPV loads.

Venous thromboembolism (VTE) is one of the major causes of pregnancy-related mortality and morbidity. This study aimed to determine the frequency of factor V Leiden (FVL) and prothrombin G20210A polymorphisms and measure the plasma levels of protein C (PC), protein S (PS) and antithrombin (AT) in pregnant women with VTE and healthy pregnant women. This prospective case-control study determined the frequencies of FVL G1691A and prothrombin G20210A polymorphisms and measured the plasma levels of PC, PS and AT in 198 pregnant women with VTE and 198 healthy pregnant women. Allele-specific polymerase chain reaction (ASPCR) was used to detect the FVL G1691A polymorphisms and prothrombin G20210A gene mutations. The FVL G1691A polymorphism and prothrombin G20210A gene mutations were detected only in pregnant women with VTE, with frequencies of 4.0 and 0.5%, respectively. The highest frequency of FVL G1691A polymorphism was observed in patients with deep vein thrombosis (DVT) and positively associated with contraceptive use and termination. Pregnant women with VTE had significantly lower levels of PC, PS and AT than those of controls. In conclusion, among the VTE cases, FVL G1691A polymorphism and PC, PS and AT deficiencies were the most common findings in patients presenting with DVT. Antithrombin deficiency was more common than PC and PS deficiencies. Contraceptive use, high body mass index (BMI) and termination correlated strongly with FVL G1691A polymorphism and PC and PS deficiencies in patients with VTE.

A case study of a 4 year old child with hypospadias and cryptorchidism on the right side is presented. Combined analysis by Karyotype and FISH showed a mosaic pattern of 48, XYYY (73%); 47,XYY (7%); 46,XY (7%) and 45,X (13%). Apart from hypospadias and cryptorchidism there were no significant phenotypic changes observed. Inheritance of this clonal abnormality was ruled out as the karyotype patterns of the child's father and brother both showed a normal karyotype. For further management, genetic counseling, and the correction of hypospadias and the undescended testis were recommended.

Although several microRNAs (miRNAs) have been associated with gastric cancer there is still the need for identification of stable and validated biomarkers. The purpose of this study was to determine the alterations of a specific set of miRNA levels in gastric adenocarcinoma tissues to identify and validate gastric cancer-specific miRNAs using paired normal and tumor samples in an independent patient cohort. Gastric adenocarcinoma and normal stomach tissue samples of 20 patients who underwent surgery for gastric cancer were studied. The miRNA expression profiling was performed for eight miRNAs in a total of 40 tissue samples using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Six out of these eight miRNAs, namely, miR-375-3p, hsamiR-129-5p, miR-196a-5p, miR-376c-3p, miR-34c-5p and miR-767-5p, were significantly underexpressed in malignant tissues of our cohort. Furthermore, the expression of miR-662 although not significantly different between normal and tumor tissues, was inversely associated with age (r = -0.440, p = 0.049). The levels of miR-129-3p and miR34c-5p were correlated with an increase in the number of metastatic lymph nodes (r = 0.470, p = 0.036; r = 0.510, p = 0.020), while and miR-376c-3p levels were negatively associated with smoking (p = 0.043). In addition, we found that the variability of miRNA expression in cancerous tissues was lower than that in normal tissues. Alterations in miRNA expression in gastric adenocarcinoma tissues in comparison to healthy tissues of each individual serves for identification of consistent biomarkers that can be used for development of diagnostic tools for gastric cancer.