Impact of COVID-19 and vaccination on first and second trimester screening results.

COVID-19 has been shown to affect pregnant women. Since pregnant women are at risk of this infection, vaccination against COVID-19 has been suggested as an imperative way to diminish rate of COVID-19 in this population. In the current observational study, we have collected data of first and second trimester screening (FTS and STS) from pregnant women who were infected with SARS-CoV-2 and/or vaccinated against COVID-19 during their pregnancy, and compared this data with a group of control pregnant women. The cohort included 4612 and 2426 women referred for FTS and STS, respectively. There was no significant difference in median values of Pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin-beta subunit (ßHCG) between infected women and controls. Moreover, these levels were not different between "Infected + vaccinated" and "Only vaccinated" groups. However, median values of PAPP-A and ßHCG were higher in "Infected + vaccinated" and "Only vaccinated" groups compared with "Infected" and "Control" groups (P < 0.001). Median values of unconjugated Estriol (uE3) and ßHCG markers were not different between "Only vaccinated" and "Control" groups, yet both markers were elevated in "Infected" and "Infected + vaccinated" groups compared with other groups. AFP values were higher in "Infected" group (P = 0.012). However, multiple of the median (MoM) and risk of open spina bifida (OSB) were not affected. Finally, median of calculated risk of trisomy 18 was lower in "Infected" and "Vaccinated" groups compared with controls (P = 0.007). Moreover, AstraZeneca and Sinopharm vaccines were associated with elevation of the calculated risk values of trisomy 21 and trisomy 18 (P < 0.001). While Sinopharm did not affect nuchal translucency (NT) and NT MoM (P = 0.13), AstraZeneca and Barakat increased and decreased these values, respectively (P values = 0.0027 and 0.015, respectively). Taken together, COVID-19 during pregnancy might be associated with some adverse obstetric outcomes. Besides, vaccination against this infection might affect the results of STS or FTS.

Clinical and Molecular Findings of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay: an Iranian Case Series Expanding the Genetic and Neuroimaging Spectra.

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS.

Incorporation of second-tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program.

BACKGROUND: Nowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non-invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC-MS/MS) for the evaluation of the baby's risk of certain metabolic disorders. METHODS: This retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second-tier tests and secondary biomarkers to improve positive predictive value (PPV). RESULTS: Statistical data were recorded via call interviewing in 6-8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false-positive rate was 0.15%. CONCLUSION: This study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second-tier tests and secondary biomarkers improves PPV of neonatal screening programs.

A novel pathogenic variant of BRAT1 gene causes rigidity and multifocal seizure syndrome, lethal neonatal.

INTRODUCTION: Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is a severe autosomal recessive epileptic encephalopathy characterized by microcephaly, rigidity, intractable focal seizures, apnea, and bradycardia at or soon after birth. RMFSL is related to BRCA1-associated ATM activator 1 (BRAT1) gene mutations. METHODS: An Iranian couple with history of infant death due to RMFSL was referred to our genetics lab for specialized genetic counseling and testing. Whole Exome Sequencing (WES) was applied. Following WES, Sanger sequencing was performed to confirm the candidate variant. RESULT: A novel nonsense variant (c.2041G > T, p. E681X) was identified in exon 14 of the BRAT1 gene. Based on the American College of Medical Genetics and Genomics guideline this variant was classified as a pathogenic variant. CONCLUSION: This research expands the spectrum of BRAT1 pathogenic variants in RMFSL syndrome and demonstrates the utility of WES in genetic diagnostic.

Personalized evolutionary hypothesis in genomics and auxiliary lymph node through diverse subtelomeric signal profile.

Few available data on the genomic-somatic evolution in breast cancer create limitation to provide the appropriate clinical managements. As an example, human subtelomeres (ST) are diverse-prone and variable targets. STs, as hot spots, have positive and negative impacts on the status of health and malady. We showed higher subtelomere signal copy number (SCN) of specific chromosomes in genomics than in auxiliary lymph node (ALN). Dissimilarity of signal intensity (SI) is found for all chromosomes. Significantly higher SI in genomics than in ALN cells were specified as chromosomes 5, 6, 9-12, 16-19 for weak; 1, 5-9, 19, X for medium; and 2, 5, 9, 10, 16, 18 for strong SI. For lacking, and presence of one and two SCNs; p/q ratio reflected differences for all chromosomes; but, 2, 3, 5, 7, 8, 10, 16, 18, 20, and X chromosomes were involved for three SCN. Chromosomes 1, 4, 9, 12, 17-19 lacked three SCN in ALN and lymphocytes. Weak SI ratio was higher in p- than in q-arm in majority of chromosomes. Manner of evolution and diversity in p- and q-arms is expressive of a novel definition as two diverse domains with a personalized insight. These data have been accompanied by periodic charts as ST array profiles which provide specific and individualized pattern in breast neoplasm. Such profiling at genomics level could be considered as a prediction through the patients' life. Moreover, subtelomere territory by interacting with protein expression of Ki67, cyclin D1, and cyclin E; and molecular targets including telomere length at genomics and somatic level provides package of information to bridge cancer cell biology to the cancer clinic as "puzzling paradigm."

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 Novel Exon 2 Deletion Mutation in the GRXCR1 Gene Associated With Non-Syndromic Hearing Loss: A Case Report and Review of Literatures.

BACKGROUND: About 80% of congenital hearing loss cases have genetic causes, often autosomal recessive and non-syndromic. Autosomal Recessive Non-syndromic hearing loss is characterized by extreme genetic heterogeneity. OBJECTIVES: To report a case of congenital hearing loss with novel homozygous deletion in GRXCR1 gene. METHODS: Case reports and review of literatures. RESULTS: In this study, the proband was a 32-year-old woman seeking pre-marriage genetic counseling with non-syndromic congenital hearing loss. An owing negative test for GJB2 mutations, she underwent exome sequencing, unveiling a novel homozygous exon 2 deletion of the GRXCR1 gene. This mutation was confirmed in her affected mother and sibling by PCR and Quantitative Real-Time PCR. CONCLUSION: We identified a novel GRXCR1 gene mutation related to congenital hearing loss in a family. Our study highlights the efficiency of exome sequencing in discovering gene mutations in cases of diseases with genetic heterogeneity.

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.

Extreme ßHCG levels in first trimester screening are risk factors for adverse maternal and fetal outcomes.

Multiples of the normal median (MoM) of free ßHCG is a valuable parameter in evaluation of risk of adverse pregnancy outcomes. In the current retrospective study, we assessed the maternal and fetal outcomes in pregnant women having free ßHCG MoM levels < 0.2 or > 5 in their first trimester screening (FTS). Relative risk of trisomy 21 was significantly higher in patients having free ßHCG MoM > 5. On the other hand, relative risk of trisomies 13 and 18 and Turner syndrome were higher in those having free ßHCG MoM < 0.2. Other chromosomal abnormalities were nearly equally detected between those having free ßHCG MoM < 0.2 or > 5. Relative risk of hydrocephaly and hydrops fetalis was higher when free ßHCG MoM was below 0.2. On the other hand, relative risk of low birth weight was higher when free ßHCG MoM was above 5. Moreover, frequency of gestational diabetes mellitus, preeclampsia, preterm delivery and vaginal bleeding increased with levels of free ßHCG MoM. However, polyhydramnios had the opposite trend. Frequencies of premature rupture of membranes and pregnancy induced hypertension were highest among pregnant women having levels of free ßHCG MoM < 0.2. The current study indicates importance of free ßHCG MoM in identification of at-risk pregnancies in terms of both fetal and maternal outcomes. In fact, ßHCG MoM < 0.2 or > 5 can be regarded as risk factors for adverse maternal or fetal outcomes irrespective of the presence of other abnormalities in the FTS results.

Niemann-Pick type A disease with new mutation: a case report.

BACKGROUND: Niemann-Pick type A (NP-A) is a congenital, hereditary disease caused by a deficiency in acid sphingomyelinase, a lysosomal enzyme. This deficiency results in an accumulation of sphingomyelin in lysosomes, leading to cellular apoptosis and ultimately to hepatosplenomegaly, neurodegenerative disorder and failure to thrive. Cherry-red spots in the macula and foamy cells in the bone marrow are other manifestations of the disease that help with diagnosis. Type A is a rare, untreatable disease with early manifestations and a poor prognosis, with newborns rarely surviving for 2-3 years. CASE PRESENTATION: A 1-year-old Persian boy was referred to our clinic due to abdominal distention and poor weight gain. He was the first male offspring of consanguineous parents. Other findings were neurodevelopmental delay, hepatosplenomegaly, severe hypotonia, difficulty in breathing, and a slightly coarse face with an open mouth and protruding tongue. The initial diagnosis was clinical mucopolysaccharidosis (MPS) based on the coarse facial features, but further workup ruled out this inherited disorder. Enzyme histochemistry revealed that the level of acid sphingomyelinase was lower than normal. In the genetic study, next-generation sequencing of all coding exons and flanking intronic regions of the patient's DNA demonstrated a homozygous c.682T>G variant in the SMPD1 gene. This variant was classified as a variant of unknown significance. Further evaluation of DNA extract from his parents and examined using Sanger sequencing showed a heterozygous c.682T>G variant in the SMPD1 gene of both parents. CONCLUSIONS: We describe a 1-year-old boy with neurodevelopmental delay, hepatosplenomegaly, and severe hypotonia. Further investigation demonstrated a new mutation for Niemann-Pick disease.

A Family With Novel X-Linked Recessive Homozygous Mutation in ANOS1 (c.628_629 del, p.1210fs∗) in Kallmann Syndrome Associated Unilateral Ptosis: Case Report and Literature Review.

OBJECTIVE: Kallmann syndrome (KS) may be accompanied by anosmia or hyposmia and midline defects. We present an overweight 16-year-old boy with a lack of puberty, anosmia, congenital right eye ptosis, and normal intellectual function. METHODS: Testicular ultrasonography was performed. Whole-exome sequencing was performed on peripheral blood specimens. Genetic results were confirmed by Sanger sequencing. Anosmia was evaluated quantitatively using the Korean version of the Sniffin' stick test II. RESULTS: Our patient presented with a complaint of lack of body hair growth and small penile size with no remarkable medical history. He was the second son of third-degree consanguineous healthy parents. Physical examination revealed pubertal Tanner stage I. Congenital right eye ptosis and obesity were noted. Anosmia was confirmed. The laboratory evaluation revealed a low serum level of testosterone, follicle-stimulating hormone, and luteinizing hormone. An X-linked recessive homozygous mutation, c.628_629 del (p.1210fs∗) in exon 5 of the ANOS1 gene was revealed and was also found in the patient's uncle and great uncle on the mother's side. CONCLUSION: To date, approximately 28 ANOS1 mutations producing KS phenotypes have been described. However, to the best of our knowledge, this particular X-linked recessive mutation has not been previously reported in KS. Furthermore, ptosis is a rare finding in KS literature. Identification of these cases increases awareness of the phenotypic heterogeneity in novel forms of KS, thereby expediting early definitive treatment, which may prevent the development of further complications.

Whole-Exome Sequencing in Idiopathic Short Stature: Rare Mutations Affecting Growth.

Idiopathic short stature (ISS) is a common diagnosis of exclusion in patients with short stature (SS). In this article, we aimed to identify the genetic causes of SS in patients with ISS and investigate treatment options. Fourteen children with diagnosis of ISS were identified, and whole-exome sequencing (WES) was subsequently conducted on blood-derived DNA. Five patients were correctly diagnosed with ISS and four had rare mutations that have not been previously reported. Four patients had mutations known to cause SS and one had a mutation that was known not to affect height. WES can help identify rare mutations implicated in ISS.

The Role of Thyroid Function Tests in Diagnosing Allan-herndon-dudley Syndrome Revisited: A Novel Iran-based Mutation.

INTRODUCTION: Allan-Herndon-Dudley Syndrome (AHDS) is a rare X-linked recessive intellectual disability condition with neuromuscular involvements. Altered thyroid function tests are major milestones in AHDS diagnosis. However, due to phenotypic variations in the levels of thyroid hormones in AHDS patients, we believe that the disorder is often underdiagnosed. Here, we reported a 3.5-year-old boy with an AHDS diagnosis and healthy thyroid hormones. METHODS: Whole-Exome sequencing followed by data analysis was performed on the patient's sample. The mutation was confirmed by Sanger sequencing in the patient and his mother. RESULTS: We reported a 3.5-year-old boy with AHDS diagnosis and a novel synonymous missense mutation (c. 1026G>A) in the SLC16A2 gene manifesting normal levels of T3, T4, and TSH. The mutation causes no change in amino acid sequence; however, it affects splicing through alteration of an exonic splicing enhancer. To the best of our knowledge, there are only 3 similar reports in the literature reporting AHDS diagnosis and normal levels of thyroid hormones. CONCLUSION: The altered levels of thyroid hormones are notable but not necessary markers for diagnosing AHDS. The candidate diagnosis of AHDS should be considered in patients with X-linked recessive intellectual disability syndrome with neuromuscular involvements irrespective of levels of thyroid hormones; otherwise, it could lead to the under-diagnosis of the disorder.

Karyotype analysis of amniotic fluid cells and report of chromosomal abnormalities in 15,401 cases of Iranian women.

The aim of present study was to assess the karyotypes of amniotic fluid cells and find the frequency of chromosomal abnormalities and their significance in clinical setting. A total of 15,401 pregnant women were assessed from March 2016 to May 2019, and 14,968 amniotic fluid samples were successfully cultured. These fetuses were grouped according to different indications including advanced maternal age, abnormal nuchal translucency (NT) values, positive first/second trimester screening results, high risk NIPT results, very low PAPP-A and free ß-hCG multiples of the normal median (MoM) results, abnormal ultrasound findings or previous history of chromosomal abnormalities. Results indicated the presence of normal karyotype in 90.2% (13,497/14,968) of fetuses. Totally, 46.4% (6945/14,968) of fetuses were 46,XX and 43.8% (6552/14,968) had 46,XY chromosome pattern. A total of 1077 abnormal karyotypes were found among 14,968 fetuses, thus the rate of abnormal fetuses was calculated to be 7.2% (1072/14,968). Meanwhile, a total of 394 cases (2.8%) had a normal polymorphism in their karyotype. In other words, abnormal karyotypes were detected in one of 13.9 cases of patients underwent amniocentesis. Down syndrome, Edward's syndrome, abnormal mosaicisms and Patau's syndrome were detected in 4.4% (659/14,968), 0.57% (85/14,968), 0.49% (74/14,968) and 0.24% (36/14,968) of cases, respectively. Sex chromosomal abnormalities including Klinefelter syndrome, Turner syndrome and 47,XXX karyotype were detected in 64 cases (0.43%). In this article, the rates of chromosomal abnormalities are compared between different groups of patients based on the advanced maternal age, abnormal NT values, very low PAPP-A and free ß-hCG MoMs results, and positive FTS results. The current investigation provides insight into the most appropriate indications for amniocentesis in Iran.

Fine-tuning of routine combined first- trimester screening: The ratio of serum-free- beta-human chorionic gonadotropin (fß-hCG) to pregnancy-associated plasma protein-A (PAPP-A) could improve performance of Down syndrome screening program, a retrospective cohort study in Iran.

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 fß-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 fß-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.

Non-invasive prenatal test to screen common trisomies in twin pregnancies.

OBJECTIVES: Recent years have witnessed a shift from invasive methods of prenatal screening to non-invasive strategies. Accordingly, non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has gained a considerable deal of interest from both geneticists and obstetricians. Efficacy of this method in identification of common aneuploidies has been extensively assessed in singleton pregnancies. However, a limited number of studies have addressed the twin pregnancies. In this context, the present study is aimed at identification of the efficacy of NIPT in twin pregnancies. METHODS: NIPT was performed on twin pregnancies to screen trisomies 13, 18 and 21. Pregnant women referring to Nilou Clinical Laboratory between March 2016 and December 2018 were included in this research. RESULTS: In the current study, a total 356 twin pregnancies were screened in search for trisomies 13, 18 and 21. 6 cases exhibited positive NIPT results in which the presence of trisomies 13, 18 and 21 was confirmed by fetal karyotype in 1, 2 and 2 cases, respectively. One twin pregnancy showed normal karyotype. The combined false-positive rate for these trisomies was 0.28%. No false negative case was observed. The combined sensitivity and specificity of NIPT in twin pregnancies were 100 and 99.7%, respectively. CONCLUSION: The results of the current study verify the feasibility, sensitivity and specificity of NIPT in twin pregnancies.

A novel nonsense mutation in the WFS1 gene causes the Wolfram syndrome.

Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder, which is mostly caused by mutations in the WFS1 gene. The WFS1 gene product, which is called wolframin, is thought to regulate the function of endoplasmic reticulum. The endoplasmic reticulum has a critical role in protein folding and material transportation within the cell or to the surface of the cell. Identification of new mutations in WFS1 gene will unravel the molecular pathology of WS. The aim of this case report study is to describe a novel mutation in exon 4 of the WFS1 gene (c.330C>A) in a 9-year-old boy with WS.

Evaluation of in vitro spermatogenesis system effectiveness to study genes behavior: monitoring the expression of the testis specific 10 (Tsga10) gene as a model.

BACKGROUND: In vitro generation of germ cells introduces a novel approach to male infertility and provides an effective system in gene tracking studies, however many aspects of this process have remained unclear. We aimed to promote mouse embryonic stem cells (mESC) differentiation into germ cells and evaluate its effectiveness with tracking the expression of the Tsga10 during this process. METHODS: mESCs were differentiated into germ cells in the presence of Retinoic Acid. Based on developmental schedule of the postnatal testis, samples were taken on the 7th, 12th, and 25th days of the culture and were subjected to expression analysis of a panel of germ cell specific genes. Expression of Tsga10 in RNA and protein levels was then analyzed. RESULTS: Transition from mitosis to meiosis occurred between 7th and 12th days of mESC culture and post-meiotic gene expression did not occur until the 25th day of the culture. Results showed low level of Tsga10expression in undifferentiated stem cells. During transition from meiotic to post-meiotic phase, Tsga10 expression increased in 6.6 folds. This finding is in concordance with in vivo changes during transition from pre-pubertal to pubertal stage. Localization of processed and unprocessed forms of the related protein was similar to those in vivo as well. CONCLUSIONS: Expression pattern of Tsga10, as a gene with critical function in spermatogenesis, is similar during in vitro and in vivo germ cell generation. The results suggest that in vitro derived germ cells could be a trusted model to study genes behavior during spermatogenesis.

Expression of Testis Specific Genes TSGA10, TEX101 and ODF3 in Breast Cancer.

BACKGROUND: Breast cancer is the most common malignancy in women around the world so finding new biomarkers for early detection and also study on molecular aspects of breast cancer is valuable. Cancer testis genes are a group of genes expressed solely in testis and in a range of human malignancies. OBJECTIVES: In this study we determined the expression of cancer testis genes Tsga10, TEX101 and ODF3 in patients with breast cancer. MATERIALS AND METHODS: Fifty patients with breast cancer were enrolled in this study. Breast cancer cell lines MCF-7 and MDA-MB-231 were also used to determine the expression of testis cancer genes. For both patients and cell lines, cancer testis genes of TSGA10, TEX101 and ODF3 were determined by RT-PCR. The presence of auto antibody against these genes in patients' serums was carried on by ELISA method. RESULTS: Seventy percent of patients showed TSGA10 expression but none of them showed expression of TEX101 and ODF3. Fourteen percent of patients were positive for anti TSGA10 but all patients were negative for anti TEX101 and anti ODF3. Both of breast cancer cell lines exhibited very strong expression of TSGA10. CONCLUSIONS: Because of the important roles of Tsga10 in cell proliferation, we concluded that this gene may have a role in proliferation and survival of breast cancer cells and could be used for diagnosis and immunotherapy of breast cancer.

Expression analysis of MiR-21, MiR-205, and MiR-342 in breast cancer in Iran.

MicroRNAs (miRNAs) are short non-coding RNA molecules characterized by their regulatory roles in cancer and gene expression. We analyzed the expression of miR-21, miR-205, and miR-342 in 59 patients with breast cancer. Samples were divided into three different groups according to their immunohistochemistry (IHC) classification: ER-positive and/or PR-positive group (ER+ and/or PR+; group I); HER2-positive group (HER2+; group II); and ER/PR/HER2- negative (ER-/PR-/HER2-; group III) as the triple negative group. The expression levels of the 3 miRNAs were analyzed in the tumor samples and the compared with the normal neighboring dissected tumor (NNDT) samples in all three groups. The expression of miR-21 was similar in all three groups. In patients positive for P53 by IHC, positive for axillary lymph node metastasis and higher tumor stages, it appeared to have significantly elevated. However, significant increase was not found among the 18 fibroadenoma samples. Both miR-205 and miR-342 expressions were significantly down regulated in group III. We conclude that miR-21 does not discriminate between different breast cancer groups. In contrast, miR-205 and miR-342 may be used as potential biomarkers for diagnosis of triple negative breast cancer.