DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture

Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction-(PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%, = 0.049; 38.15% versus 16.2%, = 0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097-3.863; = 0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041-2.129; = 0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101-1.992; = 0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR

The First Case Report of 47,XXY/46,XX/46,XY Mosaic Klinefelter Syndrome Patient With Mixed Connective Tissue Disorder

Klinefelter syndrome (KS) mosaicism 47,XXY/46,XX/46,XY is an extremely rare disorder. Mixed connective tissue disorder (MCTD) is a systemic rheumatological disease with overlapping characteristic features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM)/dermatomyositis (DM), and rheumatoid arthritis (RA). It contains a higher titer level of U1-RNP and anti-RNP antibodies. A 50-year-old man was referred to our clinic with gynecomastia, lower extremity rash, persistent fever, arthralgia, muscle weakness, dry eye and mouth, Raynaud’s phenomenon abnormal, and hormone levels. He was a follow-up patient for MCTD. Chromosome analysis of the patient revealed an abnormal karyotype of mos47,XXY/46,XX/46,XY. Fluorescence in situ hybridization (FISH) analysis indicated ish(SRYx1),(DZYx1)(DZX1x2)/ish (SRYx0),(DYZ1x0)(DZX1x2)/ish(SRYx1), (DZYx1)(DZX1x1). Although the prevalence of autoimmune diseases in Klinefelter syndrome is unknown, it is thought that the estimated frequency is higher than men, close levels to that of women. This might be explained by several genes that regulate the function of the immune system located on the X chromosome and the gene dosage mechanism that is the escape of X-inactivation in early embryogenesis for KS development. To the best of our knowledge, this is the first case to report a 47,XXY/46,XX/46,XY Klinefelter syndrome patient with MCTD

The Effect of PAI-1 Gene Variants and PAI-1 Plasma Levels on Development of Thrombophilia in Patients With Klinefelter Syndrome

Klinefelter syndrome (KS) is a common sex chromosome-related abnormality seen among men. KS negatively affects spermatogenesis and testosterone production. It increases the risk of thrombosis but its molecular mechanism has not been well described yet. Elevated PAI-1 is a risk factor for thrombosis. The rs1799889 polymorphism located in the promoter region of the PAI-1 gene was detected in patients with deep venous thrombosis. In this study, the PAI-1 gene variant and its plasma levels in KS patients were examined. Forty-one KS patients (47, XXY) and 50 age-matched healthy controls participated. DNA was isolated from peripheral blood and a real-time PCR method was used to detect known SNPs in the PAI-1 gene. In addition, PAI-1 plasma levels were measured by using ELISA method. There was no significant difference between PAI-1 gene polymorphisms of KS patients and controls (p > .05). The significant difference was observed in PAI-1 plasma levels between two groups (high PAI-1 plasma level in KS patients compared to controls). The patients' group mean was 55.13 and control group mean in PAI-1 level was 29.89 ng/ml (p = .020). Clinical features related to thromboembolism especially varicose veins were detected in KS patients frequently (p = .04). These results suggest that thromboembolism related to clinical features is seen more frequently in cases with KS, but it may not be dependent only on the PAI-1 gene polymorphism structure

Three novel mutations in 20 patients with hereditary spastic paraparesis

Hereditary spastic paraparesis (HSP) constitutes both genetic and clinically heterogeneous group of upper motor neuron diseases. Half of the individuals with autosomal dominant (AD) HSP have mutations in SPAST, ATL1, and REEP1 genes. This study was conducted to elucidate the genetic etiology of patients with the pure type AD-HSP diagnosis. The patient group consisted of 23 individuals from 6 families in Turkey. In the first step of work, Sanger sequencing (SS) was performed in ATL1, SPAST, and REEP1 genes and the second phase whole-exome sequencing (WES) was performed following SS analysis for the patients with no detected mutations in these genes. The results of this study revealed that in ATL1, 6 patients have previously reported c.776C > A mutation and 6 patients have novel c.470 T > C mutation. In SPAST, 3 patients have novel c.1072G > C mutation and 2 patients have novel c.1099-1G > C mutation. WES was performed in three patients, who had no detected mutation in these genes with SS analysis. In this approach, as previously reported c.1859 T > C mutation in KIAA0196 was detected, and it was confirmed with the patient's relatives by SS. In three of patients, no HSP-associated variant could be identified in SS and WES. With this study, the molecular genetic etiology in 20 of 23 (87%) individuals that were included in this study with the utilization of SS and WES was elucidated. Utilization of SS and WES methods have enabled the identification of genetic etiology of HSP further with appropriate genetic counseling that was provided to the patients

The effect of medicarpin on PTEN/AKT signal pathway in head and neck squamous cell carcinoma

Background/Aim: We aimed to investigate the in vitro modulating effects of medicarpin on the PI3K/AKT signal pathway gene expressions in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The effect of medicarpin on PTEN and other associated genes in the PTEN/AKT signal pathway was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, real-time quantitative polymerase chain reaction, and Western blot analysis in the SCCL-MT1 (HNSCC) and control (HEK-293) cell lines. Results: The IC50 dose was 80 mu M as a result of medicarpin treatment on HNSCC cells (P = 0.0006). It was found that PTEN and AKT gene expressions increased after the medicarpin administration while PDK1 gene expression was decreased in SCCL-MT1 cells (P = 0.0002, P = 0.0003, and P = 0.05, respectively). Protein expression results showed that medicarpin-treated cells significantly increased in pAKT (P = 0.024), pPTEN (P = 0.032), and decreased pPDK1 (P = 0.059) in SCCL-MT1. Conclusions: Our data show that medicarpin modulates HNSCC cells by increasing the PTEN and decreasing PDK1 expressions. PDK1 gene expression effects mTOR pathway which may increase AKT gene. Our study suggests that both medicarpin extracts combination with the HNSCC drug may be more effective in cancer treatment. Future prospective studies that integrate molecular and pharmacogenetic studies are crucial for revealing the mechanism and preventive medical efforts

Selection of reliable reference genes for qRT-PCR analysis on head and neck squamous cell carcinomas.

The choice of reliable reference genes as an internal control is inevitable to obtain accurate results. Here we present an assessment of 7 reference genes (18S rRNA, 28S rRNA, ACTB, GAPDH, TUBA1, YWHAZ, and SDHA) to normalize gene expression data in Head and Neck Squamous Cell Carcinomas (HNSCCs). We attempted to determine a reliable set of reference genes to use in the normalization of gene expression data in Head and Neck Squamous Cell Carcinomas (HNSCCs) and normal mucosal tissues. Malignant and non-malignant tissue samples were collected from 12 patients with primary untreated HNSCC. geNorm and NormFinder software packages were used for data evaluations. Results obtained by geNorm indicated that average expression stability values (M) of all candidates genes were smaller than 1.5 (accepted M value for geNorm), showing that all the evaluated genes can be employed as HKGs, although GAPDH and ACTB were reported to be the most stable. Similarly, NormFinder results were in agreement with geNorm's results. GAPDH and ACTB are considered to be most suitable reference genes to evaluate novel gene expression in the tissues several of HNSCCs