Deletions within the male-specific region of the Y-chromosome, known as Y-Chromosome Microdeletions (YCMs), are present in as many as 5% and 10% of severe oligospermic and azoospermic men, respectively. These microdeletions are distinguished by which segment of the Y chromosome is absent, identified as AZFa (the most proximal segment), AZFb (middle), and AZFc (distal). The reported prevalence of YCMs within the world's populations of infertile men displays vast heterogeneity, ranging from less than 2% to over 24% based on region and ethnicity. AZFc is the most commonly identified YCM, and its phenotypic presentation provides for the highest chance for fertility through artificial reproductive techniques. Conversely, deletions identified in the subregions of AZFa, AZFb, or any combination of regions containing these segments, are associated with low probabilities of achieving pregnancy. A putative mechanism explaining this discrepancy lies within the expression of autosomal, DAZ-like genes which could serve to "rescue" wild type AZFc gene expression and hence spermatogenesis. Nevertheless, recent reports challenge this dogma and stress the importance of further analysis when an AZFb deletion is detected. The screening thresholds to determine which oligospermic and azoospermic men are tested for potential YCMs has been recently contested. More recent literature supports lowering the threshold from 5 million sperm/mL of ejaculate to 1 million/mL as the frequency of YCMs in men with sperm concentrations between 1 and 5 million sperm/mL is very low (~0.8%). As such, subsequent guidelines should recommend a lower screening threshold. While YCMs are extremely common globally, the understanding of their clinical significance in the field remains scattered and without consensus. Furthermore, very little is currently known about partial deletions within the AZFc region, such as b1/b3, b2/b3, and gr/gr. Hence, this review aimed to summarize and discuss modern trends in the epidemiology, screening guidelines, and clinical considerations pertaining to YCMs.

/pdf/y-chromosome-microdeletions-a-review-of-prevalence-screening-3e2qtemydr.pdf

Y-Chromosome Microdeletions: A Review of Prevalence, Screening, and Clinical Considerations.

Purpose: A proportion of cases with repeated abortion are caused by chromosomal abnormality in one of the parents. The purpose of this study was to assess the frequency and nature of chromosomal aberrations that contribute to the occurrence of recurrent miscarriages. Several studies have been done to determine the role of chromosomal abnormalities in couples with recurrent spontaneous abortion in various countries. None of these studies was done in Morocco. Material and Methods: Cytogenetic study was done for 238 Moroccan couples who presented with repeated abortion at the Institut Pasteur, Casablanca, Morocco. Results: We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 13 (6.1%) of 238 couples. twelve of chromosomal abnormalities were structural and one of them were numerical. Conclusion: This study highlights the importance of constitutional cytogenetic exploration of couples with a history of repeated spontaneous abortion. Cytogenetic findings could provide valuable information for genetic counseling and allow monitoring of future pregnancies by prenatal diagnosis in couples with a history of recurrent miscarriage.

/pdf/chromosomal-abnormalities-in-238-couples-with-recurrent-2xh9yjytlt.pdf

Chromosomal Abnormalities in 238 Couples with Recurrent Miscarriages in Morocco

Colorectal cancer (CRC) is the leading malignant tumor in terms of morbidity and mortality worldwide, and its pathogenesis involves multiple factors, including environment, lifestyle, and genetics. Continuing evidence suggests that circular RNAs (circRNAs), as a novel non-coding RNA, constitute an important genetic variable in the pathogenesis of CRC. These circRNAs with covalently closed-loop structures exist objectively in organisms. They not only have the biological functions of regulating the expression of target genes, changing the activity of proteins, and translating proteins, but also play a key role in the proliferation, invasion, migration, and apoptosis of tumor cells. CRC is one of the most common cancers in which circRNAs are involved in tumorigenesis, metastasis, and drug resistance, and circRNAs have been demonstrated to function through crosstalk with multiple signaling pathways. Therefore, this review summarizes the biological and carcinogenic functions of circRNAs and their related PI3K/AKT, MAPK, Notch, JAK/STAT, Hippo/YAP, WNT/β-catenin, and VEGF signaling pathways in CRC. We further explore the clinical value of circRNAs and important signaling proteins in the diagnosis, prognosis, and treatment of CRC.

/pdf/mechanisms-and-prospects-of-circular-rnas-and-their-192wq98k.pdf

Mechanisms and prospects of circular RNAs and their interacting signaling pathways in colorectal cancer

To evaluate pregnant women's knowledge about features of the second-trimester screening for Down syndrome and to assess if knowledge and educational level influence attitude towards amniocentesis prior to receiving test results Three hundred pregnant Caucasian women younger than 35 years with no personal and/or family history of Down syndrome were surveyed Women were randomized in two groups One group of 150 women were surveyed by questionnaire prior to consultation with specially trained midwives, and another group of 150 women were surveyed after consultation The questionnaire consisted of three sections: 1) demographic data of participants, 2) knowledge about prenatal screening for Down syndrome, 3) readiness to undergo amniocentesis for increased risk of Down syndrome Women surveyed after consultation had greater total knowledge scores than those surveyed before consultation (p<0001) A statistically significant difference in knowledge scores in relation to educational levels was observed only in women who were surveyed before consultation (p=0007) Significantly more women were prepared to accept amniocentesis in the group surveyed after consultation (74%) than before consultation (53%) (p<0001) Knowledge gained during prescreening consultation influenced pregnant women's attitudes towards further diagnostic investigation A smaller proportion of women who were indecisive were obtained in the group surveyed after pre-screening consultation Their indecisiveness was not affected by poor knowledge about screening, but rather by a difficulty to respond how they will feel and decide in the future if screening result will be positive

Pregnant women's attitudes towards amniocentesis before receiving Down syndrome screening results

The preauricular sinus (PAuS) is a congenital foramen, opening or invagination, usually located on the crus of the auricular helix and is considered a congenital malformation and component of multiple syndromes The structure can be present unilaterally or bilaterally, with the possibility of more than one fistula present on one ear, predominantly on the auricular tags As a well-defined and established clinical entry, PAuS has a very strictly laid-out history However, different works of art give us a glimpse into the structure before its first true clinical description, showing that the PAuS was known to man long before it was first clinically described, such as those of Hieronymous Bosch, with the first medical descriptions being attributed to Heusinger and Virchow In modern times, the condition is considered both an individual malformation and a component of several genetic syndromes

Preauricular Sinus: A Tale of Forgetful Rediscovery.

There is growing interest in single nucleotide polymorphisms (SNPs) in the genes of microRNAs (miRNAs), which could be associated with susceptibility to colorectal cancer (CRC) and therefore for prognosis of the disease and/or treatment response. Moreover, these miRNAs-SNPs could serve as new, low-invasive biomarkers for early detection of CRC. In the present article, we performed a thorough review of different SNPs, which were investigated for a correlation with the CRC risk, prognosis, and treatment response. We also analyzed the results from different meta-analyses and the possible reasons for reported contradictory findings, especially when different research groups investigated the same SNP in a gene for a particular miRNA. This illustrates the need for more case-control studies involving participants with different ethnic backgrounds. According to our review, three miRNAs-SNPs—miR-146a rs2910164, miR-27a rs895819 and miR-608 rs4919510—appear as promising prognostic, diagnostic and predictive biomarkers for CRC, respectively.

/pdf/single-nucleotide-polymorphisms-in-microrna-genes-and-2s6w5sia.pdf

Single Nucleotide Polymorphisms in microRNA Genes and Colorectal Cancer Risk and Prognosis

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.

https://www.mdpi.com/2072-6694/13/14/3395/pdf

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer.

Objective: For the past several years the screening and diagnostic tests for Down syndrome have evolved rapidly with the introduction of the non-invasive prenatal testing. However, not all of the women are aware of new test options. That is why the aim of our survey is to investigate the women’s awareness towards prenatal Down syndrome tests in Bulgaria.

Methods: А survey was conducted among 500 randomly selected females from 18 to 47. It was designed as a prospective study carried out both online and at the genetic counseling office in the Laboratory of Medical Genetics, Varna. All the information was collected between January 2018 and June 2018.

Results: 384 (76.3%) of the women received information about the different tests option from their obstetrician. The rest 116 (23.7%) were self-educated. In total 345 (68.5%) of the females were satisfied with the Down syndrome tests information provided by their obstetrician. They had better knowledge of what biochemical screening is - 128 (25.4%) marked very good and 207 (41.2%) - good . When asked about the NIPT test, 202 (40.2%) did not know what NIPT was. 222 (44.4%) defined their knowledge about the amniocentesis as very good or good. However, only 65 (13.0%) would definitely undergo this procedure, if indicated. According to the results, for 346 (68.8%) women the accuracy of the test is most important when choosing a method for Down syndrome testing. Although the price was placed third as a factor for preferring a prenatal Down syndrome test, almost 80% of the questioned women said that they are willing to pay no more than 150 euros.

Conclusion: The results from the survey demonstrate the lack of knowledge about the offered screening and diagnostic tests for Down syndrome, especially NIPT. Better education and counseling of women during their pregnancy consultations are recommended

https://www.longdom.org/open-access/womens-awareness-towards-prenatal-down-syndrome-tests-in-bulgaria.pdf

Women's Awareness Towards Prenatal Down Syndrome Tests in Bulgaria

Introduction Reproductive failure (RF) includes a variety of problems such as infertility, recurrent miscarriages, stillbirths, the birth of children with multiple birth defects, and/or mental retardation. Chromosomal aberrations in one of the partners (in 2-8%) are considered to be one of the causes of reduced fertility in couples of reproductive age. Aim The aim of this study was to evaluate the effect of the chromosomal abnormalities in families with reproductive failure (RF) in the Bulgarian population. Materials and Methods A total of 1733 patients with unexplained RF, who visited the Laboratory of Medical Genetics–Varna, Bulgaria, between January 2004 and December 2019, were investigated by conventional cytogenetic analysis GTG differential banding technique. Approximately 10 metaphases were karyotyped for each patient on the resolution 400-550 GTG bands. Results Chromosomal abnormalities were found in 110/1733 infertile patients (6.35%), and the percentage of women (4.33%) was statistically significant (p <0.0001), higher than that of men (2.02%). Most of the chromosomal abnormalities were found in patients with a combined reproductive history (40.9%, 45/110). Regarding the type of chromosomal abnormality, the structural aberrations (63.7%) were almost twice as many as the numerical (33.6%). The percentage of combined abnormalities was very low (2.72%). The numerical aberrations found by us included only sex chromosomes, and in 91.9% they were presented in a mosaic variant. Of these, 88.2% were affected females (p <0.0001). A complete form of sex chromosome aneuploidy was found in only 3 individuals, all males. Of the structural aberrations, 88.6% were in full form, of which the most common was translocation (82.3%). Conclusion RF is a socially significant problem, as the relative share of couples with reproductive disorders worldwide, as well as in Bulgaria, is constantly growing. The results of our study contribute to the detection of the causes in 6.35% of couples with RF in Bulgaria and present the undeniable benefit of conducting conventional cytogenetic analysis in such couples.

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Cytogenetic findings of couples with reproductive failure – retrospective analysis from Bulgarian Population

Objective To analyze the role of 14 base pair (bp) insertion (ins)/deletion (del) and tumour necrosis factor alpha (TNF-α) G/A polymorphisms as risk factors for spontaneous miscarriage in patients with two or more unsuccessful pregnancies and a group of control women with at least two normal live births. Materials and Methods To investigate the role of these mutations, 50 patients with two or more idiopathic recurrent miscarriages and 50 normal fertile women were tested for the presence of human leucocyte antigen-G (HLA-G) 14 bp ins/del and TNF-α -308 G/A variants. The frequencies of the studied polymorphisms were compared between the two groups. Results Individuals with a history of miscarriages had a significantly higher prevalence of 14 bp insertion alleles compared with control patients (p=0.04). There was also a two times higher relative risk for miscarriage among carriers of this variant. No statistical difference in allele frequencies of the TNF-α -308 G/A polymorphism was established between controls and study patients (p=0.78). Conclusion The 14 bp ins HLA-G variant could be associated with a higher risk for unsuccessful pregnancy according to the results from the study. There is no association between the studied TNF-α -308 GA polymorphism and rate of spontaneous abortions.

Association between polymorphic markers human leucocyte antigen-G and tumour necrosis factor alpha and susceptibility to recurrent miscarriages among Bulgarian women.

Mariya Levkova

Papers

Single Nucleotide Polymorphisms in microRNA Genes and Colorectal Cancer Risk and Prognosis

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer.

Women's Awareness Towards Prenatal Down Syndrome Tests in Bulgaria

Cytogenetic findings of couples with reproductive failure – retrospective analysis from Bulgarian Population

Association between polymorphic markers human leucocyte antigen-G and tumour necrosis factor alpha and susceptibility to recurrent miscarriages among Bulgarian women.