Diagnostic potential of microRNAs Mi 517 and Mi 526 as biomarkers in the detection of hypertension and preeclampsia in the first trimester

Objectives: MicroRNAs have been observed to play a major role in various physiological processes, for instance, programmed cell death, cell division, pregnancy development, and proliferation. With the help of profiling of microRNAs in the serum of pregnant women, it is possible to link alterations in their concentration to the emergence of gestational problems. The aim of the study was to evaluate the diagnostic potential of MicroRNAs Mi 517 and Mi 526 as biomarkers in the detection of hypertension and preeclampsia.  Material and methods: The study considered 53 patients who are in their first trimester of a singleton pregnancy. Participants have been divided into two study groups, one group with normal pregnancy and another group having the risk of developing preeclampsia or who developed hypertension or preeclampsia during follow-up constitute the study group. In order to collect data associated with circulating miRNAs in serum, blood samples have been collected from the participants of the study.   Results: Based on the univariate regression model, increased expression of Mi 517 and 526 and parity status (primapara/multipara) has been obtained. The multivariate logistic analysis shows that independent risk factors for hypertension or preeclampsia are the presence of an R527 and being a primipara. Conclusions: The study's findings have revealed that R517s and R526s act as major indicative biomarkers in the first trimester for the detection of hypertension and preeclampsia. The circulating C19MC MicroRNA was examined as a potential early indicator of preeclampsia and hypertension in pregnant individuals

The Role of Cluster C19MC in Pre-Eclampsia Development

Pre-eclampsia is a placenta-related complication occurring in 2–10% of all pregnancies. miRNAs are a group of non-coding RNAs regulating gene expression. There is evidence that C19MC miRNAs are involved in the development of the placenta. Deregulation of chromosome 19 microRNA cluster (C19MC) miRNAs expression leads to impaired cell differentiation, abnormal trophoblast invasion and pathological angiogenesis, which can lead to the development of pre-eclampsia. Information was obtained through a review of articles available in PubMed Medline. Articles on the role of the C19MC miRNA in the development of pre-eclampsia published in 2009–2022 were analyzed. This review article summarizes the current data on the role of the C19MC miRNA in the development of pre-eclampsia. They indicate a significant increase in the expression of most C19MC miRNAs in placental tissue and a high level of circulating fractions in serum and plasma, both in the first and/or third trimester in women with PE. Only for miR-525-5p, low levels of plasma expression were noted in the first trimester, and in the placenta in the third trimester. The search for molecular factors indicating the development of pre-eclampsia before the onset of clinical symptoms seems to be a promising diagnostic route. Identifying women at risk of developing pre-eclampsia at the pre-symptomatic stage would avoid serious complications in both mothers and fetuses. We believe that miRNAs belonging to cluster C19MC could be promising biomarkers of pre-eclampsia development

Molecular and clinical characterization of new patient with 1,08 Mb deletion in 10p15.3 region

Abstract Background Three distinct contiguous gene deletion syndromes are located at 10p chromosomal region. The deletion, involving 10p15.3 region, has been characterized by (DeScipio et al., Am J Med Genet A 158A:2152-61, 2012). However, because of the variation in size of the described deletions and lack of knowledge about the involved genes, the correlation between genotypes and patients’ phenotypes remains unknown. Case presentation We describe female patient with de novo 1,08 Mb deletion in 10p15.3 region, similar to the patient nr seven reported by (DeScipio et al., Am J Med Genet A 158A:2152-61, 2012) but with more severe clinical features. Our patient demonstrated speech and motor delay, dysmorphic features, brain abnormalities and Tetralogy of Fallot with pulmonary atresia. Conclusions This case shows the importance of collection of more patients with deletion in order to obtain a more precise physical map of 10p region

Expanding the genetic cause of multiple sulfatase deficiency: A novel SUMF1 variant in a patient displaying a severe late infantile form of the disease

Jaszczuk I, Schlotawa L, Dierks T, et al. Expanding the genetic cause of multiple sulfatase deficiency: A novel SUMF1 variant in a patient displaying a severe late infantile form of the disease. MOLECULAR GENETICS AND METABOLISM. 2017;121(3):252-258.Multiple sulfatase deficiency (MSD) is a rare inherited metabolic disease caused by defective cellular sulfatases. Activity of sulfatases depends on post-translational modification catalyzed by formylglycine-generating enzyme (FGE), encoded by the SUMF1 gene. SUMF1 pathologic variants cause MSD, a syndrome presenting with a complex phenotype. We describe the first Polish patient with MSD caused by a yet undescribed pathologic variant c.337G>A [p.Glu113Lys] (i.e. p.E113K) in heterozygous combination with the known deletion allele c.519 +5_519 + 8del [p.Ala149_Ala173del]. The clinical picture of the patient initially suggested late infantile metachromatic leukodystrophy, with developmental delay followed by regression of visual, hearing and motor abilities as the most apparent clinical symptoms. Transient signs of ichthyosis and minor dysmorphic features guided the laboratory workup towards MSD. Since MSD is a rare disease and there is a variable clinical spectrum, we thoroughly describe the clinical outcome of our patient. The FGE-E113K variant, expressed in cell culture, correctly localized to the endoplasmic reticulum but was retained intracellularly in contrast to the wild type FGE. Analysis of FGE-mediated activation of steroid sulfatase in immortalized MSD cells revealed that FGE-E113K exhibited only approx. 15% of the activity of wild type FGE. Based on the crystal structure we predict that the exchange of glutamate-113 against lysine should induce a strong destabilization of the secondary structure, possibly affecting the folding for correct disulfide bridging between C235-C346 as well as distortion of the active site groove that could affect both the intracellular stability as well as the activity of FGE. Thus, the novel variant of the SUMF1 gene obviously results in functionally impaired FGE protein leading to a severe late infantile type of MSD. (C) 2017 Elsevier Inc. All rights reserved

Analysis of Circulating C19MC MicroRNA as an Early Marker of Hypertension and Preeclampsia in Pregnant Patients: A Systematic Review

Preeclampsia and hypertension complicate several pregnancies. Identifying women at risk of developing these conditions is essential to establish potential treatment modalities. Biomarkers such as C19MC microRNA in pregnant patients wopuld assist in defining pregnancy surveillance and implementing interventions. This study sought to analyze circulating C19MC microRNA as an early marker of hypertension and preeclampsia in pregnant patients. A systematic review was undertaken using the following registers: disease registries, pregnancy registries, and pregnancy exposure registries, and the following databases: PubMed, CINAHL, Web of Science, Scopus, and EMBASE. The risk of bias was assessed using the Cochrane technique. From the 45 publications retrieved from the registers and databases, only 21 were included in the review after the removal of duplicates, screening, and eligibility evaluation. All 210 publications had a low risk of bias and illuminated the potential use of circulating C19MC microRNA as an early marker of hypertension and preeclampsia in pregnant patients. Therefore, it was concluded that C19MC microRNA can be used as an early marker of gestational preeclampsia and hypertension