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OBJECTIVES: To evaluate the performance of the current national screening policy for Down syndrome (DS) in Iran and suggest a more efficient protocol with a wealth of a large series of first-trimester screening (FTS) data obtained from Nilou medical laboratory. To fulfill this aim, detection rate (DR), positive screening rate (PSR), false negative rate (FNR) and odds of being affected given a positive results (OAPR) were calculated at different cutoff risk. In the latest update of DS screening program in Iran, there is no place for intermediate group to be further investigated. Next, we proposed a novel parameter namely the ratio of fβ-hCG multiple of the median (MoM) value to PAPP-A MoM value to delicately categorize FTS results in a way that reduce FNR without imposing unnecessary anxious and extra money on most families. METHODS: The present investigation was conducted retrospectively on 197,210 pregnancies undergoing FTS for aneuploidies in Nilou medical laboratory, Tehran, Iran, from March 2015 to February 2016. RESULTS: Intermediate risk group is important as 23 out of 45 FN fell in the range 1:250 to 1:1100. By applying the proposed index, the ratio of fβ-hCG MoM to PAPP-A MoM and subsequent decision about NIPT, 8 out of 23 FN cases in intermediate group could be detected. CONCLUSION: Compared with the current policy, our novel proposed approach had better performance and could be applied by the Iran National Health Service to improve the screening program guideline.

Aim: Cancer-testis antigens (CTAs) have specific expression in gametogenic tissues and aberrant expression in cancers. Materials & methods: We assessed expression of five testis-specific genes namely KIF2B, CST8, TMEM225, RBM46, OAZ3 in bladder cancer tissues, adjacent non-neoplastic tissues and urinary cell pellets (UCPs) of bladder cancer patients compared with nonmalignant conditions.Results: Expressions of all CTAs were higher in UCPs of bladder cancer patients compared with nonmalignant conditions. RBM46 expression in UCPs was higher in patients with recurrent tumors compared with primary tumors and in patients without hematuria compared with those having hematuria. TMEM225 expression in tumoral tissues was higher in high-grade tumors compared with low-grade tumors. Conclusion: Expression analysis of CTAs in UCP might provide diagnostic information about bladder cancer.

Fatemeh Yazarlou,1 Mohammad Hossein Modarressi,1 Seyed Javad Mowla,2 Vahid Kholghi Oskooei,3 Elahe Motevaseli,4 Leila Farhady Tooli,5 Leila Nekoohesh,6 Maryam Eghbali,1 Soudeh Ghafouri-Fard,3 Mandana Afsharpad7 1Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran; 3Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Microbiology, School of Biology, College of Science, Tehran University, Tehran, Iran; 6Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 7Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran Background: Long non-coding RNAs (lncRNAs) and exosomes have been regarded as components of cell signal transmission that modulate indigenous cellular microenvironments. Exosomes also participate in relocation of functional lncRNAs between cells. Methods: In the present study, we evaluated expression of LINC00355, LINC00958, UCA1-201, UCA1-203, and MALAT1 lncRNAs in urinary exosomes isolated from transitional cell carcinoma (TCC) of bladder, non-malignant urinary disorders, and normal subjects. Results: LINC00355, UCA1-203, and MALAT1 expression was significantly higher in TCC patients compared to controls (non-malignant or normal samples). However, UCA1-201 expression was significantly decreased in TCC patients compared with controls. LINC00355 and MALAT1 expression was significantly lower in cigarette smokers and opium-addicted TCC patients, respectively. On the other hand, LINC00355 expression tended to be higher in opium-addicted TCC patients. The proposed panel of lncRNAs (composed of UCA1-201, UCA1-203, MALAT1, and LINC00355) had 92% sensitivity and 91.7% specificity for diagnosis of bladder cancer from normal samples. Conclusion: Transcript levels of lncRNAs in urinary exosomes are potential diagnostic biomarkers in bladder cancer. Keywords: lncRNA, exosome, bladder cancer

Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare autosomal recessive disease characterized by pain insensitivity, frequent intermittent fevers, anhidrosis, self-mutilating actions and mental retardation. Germline mutations in NTRK1 gene have been associated with CIPA. In the current study, we describe the first reported case from Iran. The patient was a 10 month old girl born to a healthy consanguineous Iranian parent with family history of CIPA. Unexpectedly, the cases had normal sweating. Whole exome sequencing revealed a new likely pathogenic mutation in the exon 13 of NTRK1 gene (NM_002529.3) in the proband in homozygote state (c.1524_1531dupGGACATCG, p.Val511Glyfs*39). The frameshift mutation leads to early termination of the coding sequence, which is anticipated to affect the protein function. Sanger sequencing confirmed the results in the proband and other affected members of the family. In addition, Sanger sequencing showed that parents carry the same mutation in heterozygote state. The current study shows a different phenotypic variant of CIPA in Iranian population and adds to the repository NTRK1 mutations.

The X-linked ZMYM3 gene (also known as ZNF261) contains the longest STR, (GA)32, identified in a human protein-coding gene 5'UTR (ENST00000373998.5: ZMYM3-207). This STR reaches maximum length in human, and is located in a complex string of four consecutive GA-STRs with a human-specific formula across the complex. A previous study in Iranian male schizophrenia (SCZ) patients revealed co-occurrence of the extreme short and long alleles of the STR with SCZ. Here we studied the allelic distribution of this STR in bipolar disorder (BD) type I. The interval encompassing the human ZMYM3 STR complex was PCR-amplified and sequenced in 546 male subjects, consisting of 157 BD patients and 389 controls.We found three alleles at the extreme short (17-repeat) and long (38- and 43-repeat) ends of the allele distribution curve in the BD cases (4.4% of the BD alleles) that were not detected in the controls (Mid p0.0001). These alleles overlapped with the extreme disease-only alleles detected previously in the SCZ patients. Domain reconstruction of the GA-STR complex revealed significant structural alteration as a result of various sequence repeats and nucleotide compositions at the inter and intraspecies levels.The ZMYM3 "exceptionally long" 5' UTR STR findings may alter our perspective of disease pathogenesis in psychiatric disorders, and set an example in which the low frequency alleles at the extreme short and long ends of the human STRs are, at least in part, a result of natural selection against these alleles and their unambiguous link to major human disorders.

Fatemeh Yazarlou,1 Seyed Javad Mowla,2 Vahid Kholghi Oskooei,3 Elahe Motevaseli,4 Leila Farhady Tooli,5 Mandana Afsharpad,6 Leila Nekoohesh,7 Nafiseh Sadat Sanikhani,4 Soudeh Ghafouri-Fard,3 Mohammad Hossein Modarressi1 1Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Faculty of Biological Sciences, Department of Genetics, Tarbiat Modares University, Tehran, Iran; 3Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Microbiology, School of Biology, College of Science, Tehran University, Tehran, Iran; 6Cancer Control Research Center, Cancer Control Foundation, Iran University of Medical Sciences, Tehran, Iran; 7Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Background: Exosomes have been regarded as emerging tools for cancer diagnosis. Tumor-derived exosomes contain molecules that enhance cancer progression and affect immune responses. Material and methods: In the present study, we evaluated expression of seven cancer-testis antigens (CTAs) that are regarded as putative biomarkers and immunotherapeutic targets along with NMP22 in urinary exosomes of bladder cancer patients, healthy subjects and patients affected with nonmalignant urinary disorders. Results: Exosomal expression of MAGE-B4 was significantly higher in bladder cancer patients compared with normal samples (expression ratio=2.68, P=0.01). However, its expression was lower in bladder cancer patients compared with benign prostate hyperplasia (BPH) patients (expression ratio=0.17, P=0.01). Exosomal expression of NMP22 was significantly higher in bladder cancer patients compared with BPH patients (expression ratio=9.22, P=0.02). Expressions of other genes were not significantly different between bladder cancer patients and normal/nonmalignant samples. We found significant correlation between MAGE-A3 and MAGE-B4 expressions in exosomes obtained from controls. In addition, TSGA10 expression was correlated with expression of NMP22 in both cancer patients and controls. Conclusion: The present study provides evidences for differential expression of CTAs in urinary exosomes of bladder cancer patients and urogenital disorders and warrants further studies for assessment of their significance in cancer diagnosis and immunotherapeutic approaches. Keywords: cancer-testis antigen, bladder cancer, exosome

Testis specific protein 10 (TSGA10) is expressed in normal adult testis and has been suggested to be involved in the normal function of sperms. Tsga10 expression has a role in the protection of spermatozoa and enhancement of male fertility. This gene has a number of single nucleotide polymorphisms (SNPs). In the current study, we genotyped rs3811553, rs200902126 and rs17852533 in 156 fertile men, 150 oligospermic and 150 azoospermic men using PCR-RFLP method. The genotyping showed that all assessed individuals were homozygote for wild type allele of both rs3811553 and rs200902126. In the case of the rs17852533, although we found the three genotypes in the studied individuals, there was no significant difference in distribution of these genotypes between the study groups. The current study shows insignificance of these SNPs in male infertility. However, future studies in larger sample sizes are needed to reach conclusive results.