Prenatal diagnosis of de novo small supernumerary marker chromosome 4q (4q11-q12): A case report

Background: Small supernumerary marker chromosomes (sSMCs) are chromosomal fragments with abnormal structures found in patients with fertility problems and developmental delay. They may be detected in amniotic cell karyotypes. sSMCs are categorized as hereditary or de novo. Here, we describe a case of prenatal de novo 4q11q12 sSMC and its molecular cytogenetic features which had no apparent phenotypic abnormality. Case: The fetus of a 36-yr-old pregnant woman was detected positive for Down’s syndrome (trisomy 21) at the 16th wk of gestation. Quantitative fluorescent polymerase chain reaction technique was applied for the rapid detection of numerical aneuploidy of chromosomes X, Y, 13, 18, and 21 microsatellites. Array comparative genomic hybridization (array CGH) technique was also conducted following the karyotype analysis of amniotic cells. The karyotype analysis was also done for the parents. Quantitative fluorescent polymerase chain reaction result revealed a male fetus with a normal chromosomal pattern, while the amniocentesis karyotype analysis identified a male fetus with a marker chromosome (47, XY, +mar), and the sSMC were existing in 100% of amniocyte metaphase spreads. The parents’ normal karyotypes indicated that the sSMC was de novo. Array CGH analysis revealed a 6.48-Mb duplication at 4q11q12. Eventually, the parents decided to terminate the pregnancy by legal abortion. Conclusion: Our study highlights the importance of the application of array CGH in combination with karyotype analysis for rapid and precise prenatal diagnosis of partial aneuploidy region.  Key words: Prenatal diagnosis, Array CGH, Chromosome 4, Chromosome markers

A Complicated Maternal Death in the context of Genetic Disorder: A Case Report

Background: Investigation of the maternal cause of death and pregnancy-related death is one of the most important responsibilities of a forensic pathologist. From the public health point of view, it may help to prevent losses during and following pregnancy and save the lives of women, especially in developing countries. Methods: We report a case of maternal death with a history of neurofibromatosis type 1 who presented asymptomatic and normotensive with normal laboratory test results.Results: The first attack after delivery was associated with pulmonary edema, which led to death. Investigation during the medico-legal autopsy discovered a left suprarenal tumor with the diagnosis of pheochromocytoma, which was confirmed by further histopathology testing.Conclusion: We believe that although the association of neurofibromatosis type 1 and normotensive pheochromocytoma during pregnancy has been reported rarely, the possibility must be considered for evaluation before elective operations to adopt proper preoperative protocols

BMI1 and TWIST1 Downregulated mRNA Expression in Basal Cell Carcinoma

Background: BMI1, TWIST1 and SNAI2/SLUG have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma and BMI1 expression could identify subtypes of Merkel cell carcinoma (MCC). However, BMI1, TWIST1 and SNAI2 expression levels in basal cell carcinomas (BCCs) have not been elucidated. We hypothesized BCC could be a good model system to decipher mechanisms which inhibit processes that drive tumor metastasis. The aim of this study was to examine the mRNA expression level of BMI1, TWIST1, and SNAI2 in BCCs. Materials and Methods: Thirty-five fresh non-metastatic BCC tissue samples and seven fresh normal skin tissue samples were evaluated by real-time RT-PCR. Results: BMI1 and TWIST1 demonstrated marked down-regulation (p< 0.00l, p= 0.00l respectively), but SNAI2 showed no significant change (p=0.12). Conclusions: Previous literature has clearly demonstrated a positive association between BMI1 and TWIST1 expression and metastatic BCC, aggressive SCC and melanoma. Here, we demonstrated a negative association between BMI1 and TWIST1 mRNA expression level and BCC

Therapeutic applications of nucleic acid aptamers in microbial infections

Today, the treatment of bacterial infections is a major challenge, due to growing rate of multidrug-resistant bacteria, complication of treatment and increased healthcare costs. Moreover, new treatments for bacterial infections are limited. Oligonucleotide aptamers are single stranded DNAs or RNAs with target-selective high-affinity feature, which considered as nucleic acid-based affinity ligands, replacing monoclonal antibodies. The aptamer-based systems have been found to be talented tools in the treatment of microbial infections, regarding their promising anti-biofilm and antimicrobial activities; they can reduce or inhibit the effects of bacterial toxins, and inhibit pathogen invasion to immune cell, as well as they can be used in drug delivery systems. The focus of this review is on the therapeutic applications of aptamers in infections. In this regard, an introduction of infections and related challenges were presented, first. Then, aptamer definition and selection, with a brief history of aptamers development against various pathogens and toxins were reviewed. Diverse strategies of aptamer application in drug delivery, as well as, the effect of aptamers on the immune system, as the main natural agents of human defense against pathogens, were also discussed. Finally, the future trends in clinical applications of this technology were discussed

Identification of a Non-Stop Mutation in PAX6 Causing a Unique Presentation of Aniridia in an Iranian Family Trial

Non-syndromic aniridia (iris hypoplasia) as an autosomal dominant eye disorder results from the chromosomal abnormalities and mutations within the paired box gene 6 (PAX6). The aim of this study was to investigate on the clinical and the underlying genetic alteration in PAX6 gene in a large pedigree with five generations of Iranian family with an autosomal dominant aniridia. Here, we reported unique clinical features in terms of presenting nystagmus, ptosis, minimal iris abnormality, foveal hypoplasia and late-onset clinical limbal stem cell deficiency. Genomic DNA was extracted from the affected members and polymerase chain reaction (PCR) was conducted using specific primers to amplify coding sequence of PAX6. Then, PCR products were subjected to bidirectional dye terminator sequencing. A heterozygous transversion mutation A→T (c.1268A>T, p.*423Lext*15) in exon 13 of PAX6 was identified in all affected individuals, but not in the healthy members. This is the first report of non-stop mutation in PAX6 gene in an Iranian family accompanied with an isolated form of unusual congenital aniridia running within this family

Association of virulence gene expression with colistin-resistance in Acinetobacter baumannii: analysis of genotype, antimicrobial susceptibility, and biofilm formation

Abstract Background Acinetobacter baumannii causes difficult-to-treat nosocomial infections, which often lead to morbidity due to the development of antimicrobial drug resistance and expression of virulence genes. Data regarding the association of resistance to colistin, a last treatment option, and the virulence gene expression of A. baumannii is scarce. Methods We evaluated the MLVA genotype, antimicrobial resistance, and biofilm formation of 100 A. baumannii isolates from burn patients, and further compared the in vitro and in vivo expression of four virulence genes among five colistin-resistant A. baumannii (Cst-R-AB) isolates. Five Cst-R-AB isolates were tested; one from the present study, and four isolated previously. Results Our results showed that reduced expression of recA, along with increased in vivo expression of lpsB, dnaK, and blsA; are associated with colistin resistance among Cst-R-AB isolates. Differences in virulence gene expressions among Cst-R-AB isolates, may in part explain common discrepant in vitro vs. in vivo susceptibility data during treatment of infections caused by Cst-R-AB. Conclusions Our findings highlight the intricate relationship between colistin-resistance and virulence among A. baumannii isolates, and underscore the importance of examining the interactions between virulence and antimicrobial resistance toward efforts to control the spread of multidrug-resistant A. baumannii (MDR-AB) isolates, and also to reduce disease severity in burn patients with MDR-AB infection