A Comprehensive Overview of NF1 Mutations in Iranian Patients.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.

A comprehensive overview of SMN and NAIP copy numbers in Iranian SMA patients.

Spinal muscular atrophy (SMA) is among the most common autosomal recessive disorders with different incidence rates in different ethnic groups. In the current study, we have determined SMN1, SMN2 and NAIP copy numbers in an Iranian population using MLPA assay. Cases were recruited from Genome-Nilou Laboratory, Tehran, Iran and Pars-Genome Laboratory, Karaj, Iran during 2012-2022. All enrolled cases had a homozygous deletion of exon 7 of SMN1. Moreover, except for 11 cases, all other cases had a homozygous deletion of exon 8 of SMN1. Out of 186 patients, 177 (95.16%) patients showed the same copy numbers of exons 7 and 8 of SMN2 gene. In addition, 53 patients (28.49%) showed 2 copies, 71 (38.17%) showed 3 copies and 53 patients (28.49%) showed 4 copies of SMN2 gene exons 7 and 8. The remaining 9 patients showed different copy numbers of exons 7 and 8 of SMN2 gene. The proportions of SMA patients with different numbers of normal NAIP were 0 copy in 73 patients (39.24%), 1 copy in 59 patients (31.72%), 2 copies in 53 patients (28.49%) and 4 copies in one patient (0.5%). These values are different from values reported in other populations. Integration of the data of the SMN1/2 and NAIP genes showed 17 genotypes. Patients with genotype 0-0-3-3-1 (0 copies of SMN1 (E7,8), 3 copies of SMN2 (E7,8) and 1 copy of NAIP (E5)) were the most common genotype in this study. Patients with 0-0-2-2-0 genotype were more likely to have type I SMA. The results of the current study have practical significance, particularly in the genetic counseling of at-risk families.

Nitric oxide, 8-hydroxydeoxyguanosine, and total antioxidant capacity in human seminal plasma of infertile men and their relationship with sperm parameters.

OBJECTIVE: Oxidative stress plays a key role in the pathogenesis of male infertility. But, the adverse effects of oxidative biomarkers on sperm quality remain unclear. This study aimed to investigate the levels of nitric oxide (NO), 8-hydroxydesoxyguanosine (8-OHdG), and total antioxidant capacity (TAC) oxidative biomarkers in seminal plasma and their relationship with sperm parameters. METHODS: A total of 77 volunteers participated in the study, including fertile (n=40) and infertile men (n=37). NO, 8-OHdG, and TAC levels were measured using the ferric reducing ability of plasma, Griess reagent method and an enzyme-linked immunosorbent assay kit, respectively. RESULTS: The mean values of sperm parameters in the infertile group were significantly lower than those in the fertile group (p<0.001). The mean 8-OHdG in the seminal plasma of infertile men was significantly higher (p=0.013) than those of controls, while the mean TAC was significantly lower (p=0.046). There was no significant difference in NO level between the two groups. The elevated seminal 8-OHdG levels were negatively correlated with semen volume, total sperm counts and morphology (p<0.001, p=0.001 and p=0.052, respectively). NO levels were negatively correlated with semen volume, total sperm counts and morphology (p=0.014, p=0.020 and p=0.060, respectively). Positive correlations between TAC and both sperm count and morphology (p=0.043 and p=0.025, respectively) were also found. CONCLUSION: These results suggested that increased levels of NO and 8-OHdG in seminal plasma could have a negative effect on sperm function by inducing damage to the sperm DNA hence their fertility potentials. Therefore, these biomarkers can be useful in the diagnosis and treatment of male infertility.

The Association of miR-let 7b and miR-548 with PTEN in Prostate Cancer.

PURPOSE: This study aims to investigate the expression level of mir-let7b-3p and mir-548, which are involved in PTEN expression in tissue samples of prostate cancer patients versus benign prostate hyperplasia (BPH) and normal adjacent tissue. MATERIALS AND METHODS: Prostate cancer tissues were obtained from patients after receiving informed consent. Total RNA extraction and cDNA synthesis were performed for determining gene expression. RESULTS: Ten patients were determined to have high Gleason scores (> 7), 36 and seven samples had intermediate Gleason scores (7?) and BPH, respectively, and 40 samples were derived from normal adjacent tissue. Downreg-ulation of mir-let7b and upregulation of mir-548 expression significantly correlated with high-risk Gleason scores. CONCLUSION: The present study showed that miR-let7b and/or mir-548 can be considered as potential targets in prostate cancer therapy.

A potential clinical significance of DAB2IP and SPRY2 transcript variants in prostate cancer.

Deregulation of key signaling pathways is one of the primary phenomena in carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein kinase pathway. These elements have also been implicated in the pathophysiology of cancer. Therefore, this study is aimed to investigate the expression of all known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate tissue samples (50 prostate cancer/ matched normal tissue and 30 BPH) were collected and total RNA was extracted followed by cDNA synthesis. The expression of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and quantitative Real-time PCR. The results indicated significant down-regulation of DAB2IP transcript variant 1 in cancerous tissues compared to paired normal tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025, respectively). In addition, there was a significant negative correlation between DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 ρ =-0.24 and P = 0.045 ρ =-0.3, respectively). Interestingly, the down-regulation of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P = 0.002 ρ = 0.434). For the first time, this experiment highlights the deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer. The present study confirms and extends the previous reports through indicating transcript-specific down-regulation and significant association of DAB2IP and SPRY2 in prostate tumorigenesis.