The Impact of Maternal Predisposing Factors on Level of Maternal Serum Pregnancy-Associated Plasma Protein A and Free Subunit Human Chorionic Gonadotropin and Nuchal Translucency.

Background: This study aimed to investigate the relationship between maternal predisposing factors with the level of maternal serum pregnancy-associated plasma protein A and free subunit human chorionic gonadotropin and nuchal translucency. Materials and Methods: We performed a cross-sectional-analytical study on 762 pregnant women who referred to the Gene Azma Medical Genetics Laboratory in Isfahan for amniocentesis. All pregnant women at high risk of screening in the first trimester of pregnancy for trisomy 21 and other aneuploidy were referred to a gynecologist for amniotic fluid sampling (amniocentesis). Multiple of the means (MoM) of PAPPA ≤0.5, 0.5 ≥ MoM free ß-hCG >2.5, and NT ≥3.5 mm were considered abnormal. We used Chi-square method and Mann-Whitney U-test to compare data qualitative and quantitative, respectively. Results: In individuals with less pregnancies and deliveries, the value of abnormal NT was higher (P < 0.01, P < 0.001, respectively). On the other hand, the highest abnormal rate of NT was observed in pregnant women under 35 years (21, 84%, P < 0.012). In addition, abnormal levels of free ß-hCG are more common in women < 35 years of age (186, 66.9%, P < 0.02) and female fetuses (171, 58.8%) (P < 0.006). Conclusion: According to the results of this study, it can be said that considering the underlying factors of pregnant mothers in performing tests related to screening in the first trimester of pregnancy can lead to a reduction in false positive rates.

The Relationship between Screening Markers in the First Trimester of Pregnancy and Chromosome Aberrations.

Background: This study was designed and performed to investigate the relationship between fetal chromosome aberrations and screening markers in the first trimester of pregnancy in order to prevent the birth of infants with chromosome aberrations with early prenatal diagnosis. Methods: We conducted an analytic cross-sectional study on result of chromosomal culture of 762 pregnant women with high-risk combined screening test from December 2018 to June 2020 and analyzed by SPSS program. Results: There was a significant relationship between chromosome structural abnormalities with free beta-human chorionic gonadotropin (free ß-hCG) values equal to and higher than 1.5 multiples of the median (MoM) (P: 0.05). The highest incidence of disorder in number of chromosomes with abnormal nuchal translucency (NT) percentiles (≥99%) was seen (P < 0.001). It also shows that the cumulative number of chromosome aberrations of 25 (78.12%) occurred in individuals with a NT less than 99th percentile and at the same time a risk of 1/50≤ risk <1/10. Discussion: According to the results, Comparative Genomic Hybridization (CGH) array method is recommended to detect structural abnormalities in chromosomes in samples with NT ≥3.5. In addition, it is noteworthy that chromosomal structural abnormalities occur in free ß-hCG ≥1.5 MoM. Conclusion: Due to the frequency of chromosomal structural disorders and its effect on the incidence of fetal abnormalities, the study of chromosomal structural disorders is recommended.

Correlations between the expression of hTERT and α and ß splice variants in human brain tumors.

BACKGROUND: Astrocytomas are diffusible infiltrative and aggressive brain tumors that are extensive and heterogeneous clusters of neoplastic growths in the central nervous system (CNS). Meningioma tumors are commonly benign but may demonstrate an invasive pattern with frequent recurrences. Human telomerase reverse transcriptase (hTERT) is an unfavorable prognostic factor for several types of cancers, and there are controversies about its role. OBJECTIVES: In the present study, we investigated the relative expression of hTERT splice variants in 2 groups of brain tumors compared to non-tumor samples. MATERIAL AND METHODS: The mRNA of 40 brain tumor samples and 4 control samples was extracted; mRNA expression of hTERT α-deletion and ß-deletion variants, as well as the wild type isoform, was quantified using quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The α-deletion variant was significantly expressed in primary benign meningeal tumors (p = 0.01). The results indicate a positive correlation between the relative expression of hTERT mRNA transcript and α-deletion and ß-deletion variants in both groups of tumors (meningiomas and astrocytomas). A strong association between the expression of the full-length splice variant and the ß-deletion variant was observed in astrocytoma tumors (p = 0.045). The most significant correlations were found between the hTERT full-length and ß-deletion variants in high-grade meningiomas (p = 0.018, correlation coefficient (CC) = 0.964) and grade II astrocytomas (p = 0.015; CC = 0.580). In addition, in low grades of both types of tumors, the hTERT full-length variant and especially the α-deletion variant were the predominant isoforms. The overexpression of hTERT and ß-deletion variants in high grades of these tumors was statistically significant. Our findings indicate that α-deletion and ß-deletion isoforms are associated with high levels of full-length hTERT mRNA in both groups of brain tumor patients. CONCLUSIONS: Changes in the splicing pattern of hTERT splice variants in brain tumors and their correlation with pathological alterations in cells could be applied as diagnostic or prognostic biomarkers, or possibly as targets for cancer therapy. However, the function and biological role of hTERT splice variants remain to be clarified.

In silico analysis of SLC3A1 and SLC7A9 mutations in Iranian patients with Cystinuria.

Cystinuria is an autosomal recessive defect in reabsorptive transport of cystine and the dibasic amino acids ornithine, arginine, and lysine from renal tubule and small intestine. Mutations in two genes: SLC3A1, encoding the heavy chain rbAT of the renal cystine transport system and SLC7A9, the gene of its light chain b0, + AT have a crucial role in the diseases. In our previous studies from Iranian populations with Cystinuria totally six and eleven novel mutations respectively identified in SLC3A1 and SLC7A9 genes. In this study, we conducted an in silico functional analysis to explore the possible association between these genetic mutations and Cystinuria. MutationTaster, PolyPhen-2, PANTHER, FATHMM. PhDSNP and MutPred was applied to predict the degree of pathogenicity for the missense mutations. Furthermore, Residue Interaction Network (RIN) and Intron variant analyses was performed using Cytoscape and Human Slicing Finder softwares. These genetic variants can provide a better understanding of genotype-phenotype relationships in patients with Cystinuria. In the future, the findings may also facilitate the development of new molecular diagnostic markers for the diseases.

Meta-Analysis of the Association between GABA Receptor Polymorphisms and Autism Spectrum Disorder (ASD).

Previous studies have reported the association of GABA receptor subunits B3, A5, and G3 single-nucleotide polymorphisms (SNPs) in chromosome 15q11-q13 with autism spectrum disorders (ASDs). However, the currently available results are inconsistent. This study aimed to investigate the association between ASD and the GABA receptor SNPs in chromosomal region 15q11-q13. The association was calculated by the overall odds ratio (OR) with a 95% confidence interval (CI). We used sensitivity analyses and the assessment of publication bias in our meta-analysis. Eight independent case-control studies involving 1408 cases and 2846 healthy controls were analyzed, namely, 8 studies for GABRB3 SNPs as well as 4 studies for GABRA5 and GABRG3 polymorphisms. The meta-analysis showed that GABRB3 polymorphisms in general are not significantly associated with autism [OR = 0.846 (95% CI): 0.595-1.201, I2 = 79.1%]. Further analysis indicated that no associations were found between GABRB3 SNPs and autism on rs2081648 [OR = 0.84 (95% CI) = 0.41-1.72, I2 = 89.2%] and rs1426217 [OR = 1.13 (95% CI) = 0.64-2.0, I2 = 83%]. An OR of 0.95 (95% CI) = 0.77-1.17 was reported (I2 = 0.0%) for GABRA5 SNPs and an OR of 0.96 (95% CI) = 0.24-3.81 was obtained from GABRG3 SNPs (I2 = 97.8%). This meta-analysis provides strong evidence that different SNPs of GABA receptor B3, A5, and G3 subunit genes located on chromosome 15q11-q13 are not associated with the development of autism spectrum diseases in different ethnic populations. However, in future research, large-scale and high-quality studies are necessary to confirm the results.

Variants in Human Prostacyclin Receptor Gene in Patients with Migraine Headache.

Objective: Prostaglandin I2 receptor plays a major physiologic role in the relaxation of arterial smooth muscle and vasodilation and possibly during migraine attacks. Therefore, in this study, the coding and noncoding exons and exon-intron boundaries of Prostaglandin I2 receptor gene were examined in patients with migraine headache and healthy controls and the potential effects of identified single nucleotide variations were evaluated using direct PCR-sequencing and in silico analysis. Method : In this study, the peripheral blood samples of 50 patients and 50 controls were examined to find any mutation in coding and noncoding exons and exon-intron boundaries of PTGIR gene. DNA was extracted and all the samples were amplified by polymerase chain reaction (PCR) and sequenced. Results: In this study, the patients had a mean age of 35.235 ± 10.99 years (range, 9-60 yrs.), and female to male ratio was 4:1 in this group. The controls had a mean age of 35.058 ± 11.116 years (range, 8-59 yrs.), and female to male ratio was 3.7:1.3 in this group. Two patients had mutations in exon 2. The first mutation was located in exon 2 (at amino acid position 251) of PTGIR gene at nucleotide position c.866A > T, a synonymous variant described previously in the database. The second mutation was located in exon 2 c.867G > A, which is a missense variant. Sequence analysis revealed high occurrence of previously reported intronic variants mostly in a homozygous statue. Conclusion: The data supported the hypothesis that mutations in PTGIR gene, particularly the mutation we described, should be considered even in cases of migraine. The presence of this mutation in patients with family history raises important issues regarding genetic counselling.