Clinicopathological characteristics and BRCA1/BRCA2 pathogenic variants of patients with breast cancer.

Although BRCA genes are well-known breast cancer genes, the clinicopathological features of breast cancer patients carrying BRCA1/2 pathogenic variants have not been adequately defined. The goals of this study were to determine the distribution of BRCA1/2 variants in the Turkish population and its correlation with clinicopathological features. Clinical data of 151 women who underwent BRCA1/2 gene testing at Mersin University Medical Faculty Hospital between 2016 and 2019 were retrospectively analyzed. BRCA1/2 variants were detected as pathogenic (n = 11), variants of uncertain significance (n = 5), likely benign (n = 3), and benign (n = 81) in breast cancer cases. The BRCA1/2 pathogenic variant carriers had a higher histological grade, rate of triple- negative type, Ki-67 proliferation index, and rate of no special type carcinoma than the group without mutation (p = 0.03, 0.01, 0.04, and 0.02 respectively). We analyzed the distribution of variants we detected in women living in our region and found that pathogenic variants in patients with breast cancer were associated with high histological grade, triple-negative type, high Ki-67 proliferation index, and histological type. Studies in diverse populations are needed to establish a clinicopathological relationship with variants more easily.

Contribution of genotypes in Prothrombin and Factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia.

Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender-matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 ± 15.20; 33.89 ± 14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients.

Nonlethal Raine Syndrome in a Newborn Boy Caused by a Novel FAM20C Variant.

Raine syndrome (RS) is a rare genetic disorder characterized by osteosclerotic bone dysplasia caused by a homozygous mutation, compound heterozygous mutation, or microdeletion in the FAM20C gene. In the present study, the MiSeq next-generation sequencing platform was used to perform the FAM20C gene sequence analysis. A novel homozygous variant c.1255T>C (p.W419R) in the FAM20C gene was diagnosed, and a nonlethal RS phenotype was confirmed, thus contributing to the expansion of the nonlethal RS phenotype. Since there is limited information about rare diseases, we believe that these studies will contribute to the literature and to the understanding of how these disorders develop and progress.

An investigation of the relation between catalase C262T gene polymorphism and catalase enzyme activity in leukemia patients.

INTRODUCTION: Catalase (CAT), an antioxidant enzyme, catalyzes conversion of hydrogen peroxide to water and molecular oxygen, protecting cells against oxidative stress. The aim of this study was to investigate the possible association between CAT C262T polymorphism in the promoter region of the CAT gene and leukemia risk and to determine the relationship between CAT genotypes and CAT enzyme activities. MATERIAL AND METHODS: Genotypes of 102 cases and 112 healthy controls' genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism methods. Catalase activity was measured with the method of Aebi. RESULTS: The frequencies of the T allele among the cases and controls were 28.4% and 25.9%, respectively (p = 0.75). The frequencies of CC, CT, and TT among cases were 57.8%, 27.4%, and 14.7%, respectively, while in controls, the frequencies of CC, CT, and TT were 54.4%, 39.3%, and 6.3%, respectively, which were not significantly different. Although CAT enzyme activity was lower in leukemia patients with TT genotypes than in controls, this did not reach statistical significance (p = 0.37). CONCLUSIONS: This is the first report showing that CAT C262T polymorphism is not a genetic predisposing factor for the risk of leukemia in the Turkish population. However, additional research is needed to confirm these findings.

A Case of Ring Chromosome 18 with Single Umbilical Artery Detected During Prenatal Period.

Fetuses with a single umbilical artery have a risk of increased chromosomal anomalies and congenital malformations. Ring chromosomes are rare and the phenotypic and clinical characteristics of affected individuals show great variability depending on the quantity of the lost critical genes or gains during the formation of the ring or due to mitotic instability. Ring chromosome 18 [r(18)] is characterized by short stature, craniofacial dysmorphism, mental and motor retardation, autoimmune disorders, extremity anomalies, dermal lesions, structural heart malformations, and kidney abnormalities. In this study, the clinical findings of a female patient who had a single umbilical artery in the prenatal period and was diagnosed as de novo r(18) by molecular karyotype analysis were compared with those in the literature. A detailed ultrasonographic examination of the fetus with a single umbilical artery may enable the detection of additional anomalies and thus the early diagnosis of chromosomal anomalies may be possible with prenatal genetic analysis.

Adrenomedullin expression in aortic artery wall of diabetic rats given alpha lipoic acid.

BACKGROUND: Diabetes mellitus (DM) is a major health problem predisposing to cardiovascular diseases. The aim of this study was to investigate the effects of alpha lipoic acid (ALA) on both the arterial wall of diabetic rats and the adrenomedullin (ADM) gene expression. METHODS: Twenty-four Wistar Albino rats were divided into three groups as Control, DM + S, and DM + ALA. For DM model, a single dose of 40 mg/kg streptozotocin, for DM + ALA group, 100 mg/kg/day/4 weeks was administered. Hematoxylin & Eosin (H&E) staining was done and vascular endothelial growth factor (VEGF) was detected by immunohistochemical analysis in the artery wall. Total damage score of vessel wall (endothelial cell damage, media layer smooth muscle cell damage, and internal elastic lamina damage) and H score (immunoreactivity intensity) were calculated. Expression of ADM gene was measured by qRT-PCR. RESULTS: In DM + S group, Total damage score of vessel wall were detected by light microscopy. There were statistically significant differences between the groups Control/DM + S and DM + S/DM + ALA in terms of the vessel total damage score and H score (p < 0.005). ADM expression was increased threefold in both DM + S and DM + ALA groups compared to the control group (p < 0.05). CONCLUSIONS: ALA may have positive effect on the vessel damage in diabetic rats. However, no significant decrease in ADM expression levels was observed in diabetic rats after ALA administration and we considered that the protective effect of ALA is independent of adrenomedullin. Further studies with different doses and durations of ALA administrations are required to investigate the changes in ADM expression.

The Correlation between IL-1ß-C31T Gene Polymorphism and Susceptibility to Breast Cancer.

PURPOSE: Interleukin-1 beta (IL-1ß), a pro-inflammatory cytokine, has been shown to influence breast cancer susceptibility. The relationship between its risk of breast cancer and IL-1ß-C31T polymorphism has been demonstrated, but the results remain controversial. Therefore, our study aimed to investigate the correlation between the IL-1ß-C31T gene polymorphism and susceptibility to breast cancer. METHODS: The genotype frequencies of IL-1ß-C31T polymorphism were compared between 204 breast cancer cases and 210 controls using polymerase chain reaction and restriction fragment length polymorphism techinques. Further multivariate binary logistic regression analyses were used to assess the association between IL-1ß-C31T polymorphism and breast cancer risk. RESULTS: The frequency of the T allele of IL-1ß-C31T polymorphism in breast cancer cases was significantly higher than that in the controls (56.1% vs. 47.9%). The frequencies of genotypes CC, CT, and TT in the cases were 22.1%, 43.6%, and 34.3%, respectively, while in the control group they were 24.3%, 55.7%, and 20.0%, respectively. There was a significant difference between the prevalence of TT genotype in the 2 groups (adjusted odds ratio [OR], 2.06; 95% confidence interval [CI], 1.16-3.66; p = 0.014). Breast cancer risk increased in women with TT genotype, body mass index (BMI) ≥ 25 kg/m2 (OR, 2.19; 95% CI, 1.09-4.36), late age at first birth (OR, 2.43; 95% CI, 1.29-4.56), postmenopausal status (OR, 3.15; 95% CI, 1.39-7.16), and negative smoking history (OR, 2.52; 95% CI, 1.32-4.82). Furthermore, increase in breast cancer risk among women diagnosed with invasive ductal carcinoma was associated with CT/TT genotypes (OR, 2.82; 95% CI, 1.38-5.76). CONCLUSION: The IL-1ß-C31T polymorphism affects breast cancer susceptibility, especially in women with late age at first birth, high BMI, postmenopausal status, negative smoking history, and invasive ductal carcinoma. Our study adds to the evidence about the importance of IL-1ß-C31T polymorphism in breast cancer susceptibility.

Comparison of endometrial biopsies of fertile women and women with repeated implantation failure at the ultrastructural level.

BACKGROUND/AIM: The aim of this study was to compare the cellular properties of endometrial tissues from fertile patients and patients having at least 3 previous in vitro fertilization failures, during the implantation window. The ultrastructural evaluation of the endometrium in the implantation window may shed light on the complexity of the implantation failure paradigm. MATERIALS AND METHODS: The study involved 23 women, 14 infertile with a clinical diagnosis of repeated implantation failure (RIF) and 9 fertile, defined as the control group. Endometrial samples were examined by transmission electron microscopy (TEM). RESULTS: In the control group, secretory vacuoles and cytoplasmic projections filled with secretory material, called pinopodes, were noted; microvilli were observed on some apical surfaces; and ciliated cells were absent. In the RIF group, the number of pinopodes was remarkably lower, with some of them being immature. Moreover, decidualization of stromal cells was not frequent and fewer epithelial cells with poor secretory vacuoles were discerned. CONCLUSION: TEM analyses of endometrial samples from the RIF group revealed dramatic differences at the ultrastructural level compared to the controls, which may well be an underlying cause of their infertility.