Update of spectrum c.35delG and c.‐23+1G>A mutations on the GJB2 gene in individuals with autosomal recessive nonsyndromic hearing loss

Hearing loss (HL) is the most common birth defect and the most prevalent sensorineural condition worldwide. It is associated with more than 1,000 mutations in at least 90 genes. Mutations of the gap junction beta‐2 protein (GJB2) gene located in the nonsyndromic hearing loss and deafness (DFNB1) locus (chromosome 13q11‐12) are the main causes of autosomal recessive nonsyndromic hearing loss worldwide, but important differences exist between various populations. In the present article, two common mutations of the GJB2 gene are compared for ethnic‐specific allele frequency, their function, and their contribution to genetic HL in different populations. The results indicated that mutations of the GJB2 gene could have arisen during human migration. Updates on the spectrum of mutations clearly show that frequent mutations in the GJB2 gene are consistent with the founder mutation hypothesis.     

A novel serum extracellular vesicle protein signature to monitor glioblastoma tumor progression

Detection of tumor progression in patients with glioblastoma remains a major challenge. Extracellular vesicles (EVs) are potential biomarkers and can be detected in the blood of patients with glioblastoma. In our study, we evaluated the potential of serum-derived EVs from glioblastoma patients to serve as biomarker for tumor progression. EVs from serum of glioblastoma patients and healthy volunteers were separated by size exclusion chromatography and ultracentrifugation. EV markers were defined by using a proximity-extension assay and bead-based flow cytometry. Tumor progression was defined according to modified RANO criteria. EVs from the serum of glioblastoma patients (n = 67) showed an upregulation of CD29, CD44, CD81, CD146, C1QA and histone H3 as compared to serum EVs from healthy volunteers (P value range: <.0001 to .08). For two independent cohorts of glioblastoma patients, we noted upregulation of C1QA, CD44 and histone H3 upon tumor progression, but not in patients with stable disease. In a multivariable logistic regression analysis, a combination of CD29, CD44, CD81, C1QA and histone H3 correlated with RANO-defined tumor progression with an AUC of 0.76. Measurement of CD29, CD44, CD81, C1QA and histone H3 in serum-derived EVs of glioblastoma patients, along with standard MRI assessment, has the potential to improve detection of true tumor progression and thus could be a useful biomarker for clinical decision making.     

Molecular detection of HHV1-5, AAV and HPV in semen specimens and their impact on male fertility

Viral infections have been considered as possible destructive factors that influence male fertility. The aim of this study was to determine the prevalence of human herpes viruses 1-5 (HHV1-5), adeno associated virus (AAV) and human papilloma virus (HPV) in semen and whether these influence semen quality. DNA extraction was performed using phenol–chloroform protocol, then three different nested-PCRs were done to detect HHV1-5, AAV and HPV DNAs in the semen samples. Of 145 samples, 66 (45.5%) were positive at least for one of the viruses. The genome detection rate of HSV1/2, VZV, EBV, HCMV, AAV and HPV were zero, 2.8%, zero, 1.4%, 27.6% and 19.3%, respectively. Of 66 positive samples for these viruses, 6 (4.1% of all samples) were positive for two viruses simultaneously. Here no association was found between variations in semen parameters related to fertility and detection of VZV, HCMV, AAV and HPV DNA in semen samples. It should be noted that the prevalence of different viruses in semen, and their relevance to male infertility, differs significantly due to the genome extraction and amplification methods or due to a real variation between study populations and geographical regions.     

miRNA expression patterns in normal breast tissue and invasive breast cancers of BRCA1 and BRCA2 germ-line mutation carriers

miRNA deregulation has been found to promote carcinogenesis. Little is known about miRNA deregulation in hereditary breast tumors as no miRNA expression profiling studies have been performed in normal breast tissue of BRCA1 and BRCA2 mutation carriers. miRNA profiles of 17 BRCA1- and 9 BRCA2-associated breast carcinomas were analyzed using microarrays. Normal breast tissues from BRCA1 and BRCA2 mutation carriers (both n = 5) and non-mutation carriers (n = 10) were also included. Candidate miRNAs were validated by qRT-PCR. Breast carcinomas showed extensive miRNA alteration compared to normal breast tissues in BRCA1 and BRCA2 mutation carriers. Moreover, normal breast tissue from BRCA1 mutation carriers already showed miRNA alterations compared to non-mutation carriers. Chromosomal distribution analysis showed several hotspots containing down- or up-regulated miRNAs. Pathway analysis yielded many similarities between the BRCA1 and BRCA2 axes with miRNAs involved in cell cycle regulation, proliferation and apoptosis. Lesser known pathways were also affected, including cellular movement and protein trafficking. This study provides a comprehensive insight into the potential role of miRNA deregulation in BRCA1/2-associated breast carcinogenesis. The observed extensive miRNA deregulation is likely the result of genome-wide effects of chromosomal instability caused by impaired BRCA1 or BRCA2 function. This study''s results also suggest the existence of common pathways driving breast carcinogenesis in both BRCA1 and BRCA2 germ-line mutation carriers.     

Development of multiplex real-time quantitative PCR for simultaneous detection of Chlamydia trachomatis,Mycoplasma hominis,Ureaplasma urealyticum,and Mycoplasma genitalium in infertile women

PurposeSexually Transmitted Diseases (STDs) can cause sterility and many other problems for women planning pregnancy. Currently, almost 340 million people worldwide suffer from Sexually Transmitted Infections (STIs). This study made attempts to quickly identify STDs' most critical infectious agents using dedicated primers and probes.MethodsThe present study was done on the cervical samples of 200 infertile women. After extracting the total DNA of Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, and Mycoplasma genitalium, quantitative methods were employed to determine the rate of target bacteria using multiplex real-time PCR.ResultsThe multiplex qPCR showed the rates of 47%, 16%, 46%, and 16.5% for Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, and Mycoplasma genitalium in infertile women, respectively. In some patients, there were co-infections with two or three bacteria. The diagnostic approach used in our research could be employed as an alternative detection tool to identify the four most common STD-associated bacterial agents while detecting mixed infections.ConclusionsInfertile women with no biological problems could have their genital tract checked using this newly designed identification technique and get proper treatment for their infections as quickly as possible.     

Chemical characterization and quality assessment of some bottled water brands from the Kohgiluyeh-va-Boyer Ahmad province market,SW Iran

Recently, bottled water consumption has been increased in Iran, because of the priority change from tap water to bottled water usage; therefore, conducting studies on quality control of the bottled drinking waters seems very necessary. In this study, a comparison between the amounts of mineral elements present in 10 bottled water brands from the Kohgiluyeh-va-Boyer Ahmad Province market, SW Iran, and recommended limits by national and international standards and guidelines for drinking water was carried out, with the aim to assess the quality of bottled waters as an outdoor supply source for drinking water. The chosen bottled water brands were analyzed for more than 50 physicochemical parameters, using inductively coupled plasma optical emission spectrometry (ICP-OES), ionic chromatography (IC), hydride generation atomic absorption spectroscopy (HGAAS), spectrophotometry, titration, and conductometry standard methods. The comparison between obtained results and Iranian, United States Environmental Protection Agency (USEPA) and World Health Organization (WHO) standards and guidelines showed that all levels of analyzed parameters do not exceed the permitted limits, indicating that the bottled waters have safe quality for drinking use. Results revealed that bottled waters are a valid substitute of tap water, especially for outdoor drinking purpose. Nevertheless, the mineral elements such as Ca, Mg, Na, and K are not provided by the bottled waters in sufficient levels needed daily by human body.