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.

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.

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.

A Successful New Case of Twin Pregnancy in a Patient with Swyer Syndrome-An Up-to-Date Review on the Incidence and Outcome of Twin/Multiple Gestations in the Pure 46,XY Gonadal Dysgenesis.

BACKGROUND: The aim of the present study is to report a rare occurrence of a successful twin pregnancy in a woman with pure 46,XY gonadal dysgenesis. RESULT(S): A patient with Swyer syndrome (pure 46,XY gonadal dysgenesis) presented with a twin pregnancy after in vitro fertilization. Due to unidentified conditions, the patient developed selective intrauterine growth restriction in one of the fetuses. Twins were born at 33 weeks of pregnancy due to the risk of asphyxia. Nonetheless, the patient did not develop gonadal malignancies before the pregnancy and, despite receiving estrogen, remained amenorrheic. CONCLUSION(S): The aim of this case report is to show the course of twin pregnancy in patients with Swyer syndrome through assisted reproduction. Due to certain disorders in the development of their reproductive organs, such as the less mature uterus, such pregnancies may be associated with an increased risk. The above case report demonstrates the need to systematize methods of pregnancy management in patients with Swyer syndrome, such as: preparation for the pregnancy, assessment of the uterus, medications used, and necessary checkups. Capsule: This case report and review shows clinicians that patients with Swyer syndrome may become pregnant. Twin pregnancies may occur without any major problems through assisted reproduction.

The role of miRNA-210 in pre-eclampsia development.

MicroRNAs (miRNAs) are a class of small non-coding, single-stranded RNAs (ribonucleic acids) that play important roles in many vital processes through their impact on gene expression. One such miRNA, miR210, represents a hypoxia-induced cellular miRNA group that hold a variety of functions. This review article highlights the importance of miR-210 in the development of pre-eclampsia.KEY MESSAGEmiR-210 is a promising biomarker for monitoring pregnancy with pre-eclampsia. Overexpression of miR-210 had a negative impact on the process of cell migration and trophoblast invasion.

Novel Mutations Within Collagen Alpha1(I) and Alpha2(I) Ligand-Binding Sites, Broadening the Spectrum of Osteogenesis Imperfecta - Current Insights Into Collagen Type I Lethal Regions.

Osteogenesis imperfecta (OI) is a rare genetic disorder demonstrating considerable phenotypic and genetic heterogeneity. The extensively studied genotype-phenotype correlation is a crucial issue for a reliable counseling, as the disease is recognized at increasingly earlier stages of life, including prenatal period. Based on population studies, clusters in COL1A1 and COL1A2 genes associated with the presence of glycine substitutions leading to fatal outcome have been distinguished and named as "lethal regions." Their localization corresponds to the ligand-binding sites responsible for extracellular interactions of collagen molecules, which could explain high mortality associated with mutations mapping to these regions. Although a number of non-lethal cases have been identified from the variants located in lethal clusters, the mortality rate of mutations has not been updated. An next generation sequencing analysis, using a custom gene panel of known and candidate OI genes, was performed on a group of 166 OI patients and revealed seven individuals with a causative mutations located in the lethal regions. Patients' age, ranging between 3 and 25 years, excluded the expected fatal outcome. The identification of non-lethal cases caused by mutations located in lethal domains prompted us to determine the actual mortality caused by glycine substitutions mapping to lethal clusters and evaluate the distribution of all lethal glycine mutations across collagen type I genes, based on records deposited in the OI Variant Database. Finally, we identified six glycine substitutions located in lethal regions of COL1A1 and COL1A2 genes, of which four are novel. The review of all mutations in the dedicated OI database, revealed 33 distinct glycine substitutions in two lethal domains of COL1A1, 26 of which have been associated with a fatal outcome. Similarly, 109 glycine substitutions have been identified in eight lethal clusters of COL1A2, of which 51 have been associated with a fatal manifestation. An analysis of all glycine substitutions leading to fatal phenotype, showed that their distribution along collagen type I genes is not regular, with 17% (26 out of 154) of mutations reported in COL1A1 and 64% (51 out of 80) in COL1A2 corresponding to localization of the lethal regions.

A new family with spastic paraplegia type 51 and novel mutations in AP4E1.

BACKGROUND: Autosomal recessive mutations in the AP-4 (adaptor protein complex 4) complex subunit ϵ - 1 (AP-4E1) gene on chromosome 15q21.2 are known to cause spastic paraplegia 51 (SPG51). The exact phenotype of SPG51 remains poorly characterized, because only a few families have been reported as carriers of the mutation. In addition, a previous study identified an autosomal dominant mutation in the AP4E1 gene as being associated with persistent stuttering. The aim of the current study was to characterize the phenotype of a paediatric patient with an identified novel AP4E1 mutation presenting with significant psychomotor retardation, intellectual disability and paraplegia. METHODS: Magnetic resonance imaging was used to identify hypoplasia of the corpus callosum. The DNA sample was tested using multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). In addition, next-generation sequencing (NGS) was performed using the patient's DNA, and Sanger sequencing was performed using that of his family members. RESULTS: The phenotype was identified to be associated with a novel pathogenic variant c.942_943 + 3delinsCC in the AP4E1 gene. The patient manifested severely delayed psychomotor development, impaired global physical development and general illness. Movement disorders were evident during the neonatal period. CONCLUSIONS: The present study identifies a previously unknown disease-inducing AP4E1 gene mutation.

Three case reports of patients indicating the diversity of molecular and clinical features of 16p11.2 microdeletion anomaly.

BACKGROUND: 16p11.2 microdeletion is a known chromosomal anomaly associated mainly with neurocognitive developmental delay, predisposition to obesity, and variable dysmorphism. Although this deletion is relatively rare among the general population, it is one of the serious known genetic aetiologies of obesity and autism spectrum disorder. CASE PRESENTATION: This study presents three cases of deletions within the 16p11.2 region. Every child had mild variable craniofacial abnormalities, hand or foot anomalies and developmental and language delays. The first proband had obesity, epilepsy, moderate intellectual disability, aphasia, motor delay, hyperinsulinism, and café au lait spots. The second proband suffered from cardiac, pulmonary, and haematological problems. The third proband had motor and language delays, bronchial asthma, and umbilical hernia. Although each patient presented some features of the syndrome, the children differed in terms of their clinical pictures. Genetic diagnosis of 16p11.2 microdeletion syndrome was made in children at different ages based on multiplex ligation probe-dependent amplification analysis and/or microarray methods. CONCLUSIONS: Our reports allow us to analyse and better understand the biology of 16p11.2 microdeletion throughout development. However, the variability of presented cases supports the alternate conclusion to this presented in available literature regarding 16p11.2 deletion, as we observed no direct cause-and-effect genotype/phenotype relationships. The reported cases indicate the key role of the interdisciplinary approach in 16p11.2 deletion diagnostics. The care of patients with this anomaly is based on regular health assessment and adjustment of nervous system development therapy.

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

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.

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.

Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay.

Neurodevelopmental disorders have long been associated with chromosomal abnormalities, including microdeletions and microduplications. Submicroscopic 14q11.2 deletions involving the CHD8 and SUPT16H genes have been reported in patients with developmental delay (DD)/intellectual disability (ID) or autism spectrum disorders (ASDs) and/or macrocephaly. Recently, disruptive CHD8 mutations were described in patients with similar phenotypes further showing pivotal role of CHD8 gene in the pathogenesis of DD/ID or ASDs. We report here the first case of ~445 kb de novo microduplication, encompassing the minimal critical 14q11.2 deletion region, in 8-year-old boy showing DD, cognitive impairment and facial dysmorphism. Our results suggest that gain of the chromosomal region 14q11.2 is causative for clinical findings present in the patient.

Structural and numerical abnormalities resolved in one-step analysis: the most common chromosomal rearrangements detected by comparative genomic hybridization in childhood acute lymphoblastic leukemia.

Comparative genomic hybridization (CGH) is a technique that permits detection of chromosomal imbalances. This method allows the detection of gains and losses of genetic material at a resolution lower than 5 Mb. The limitations of conventional cytogenetic studies, such as morphologically insufficient quality of metaphases or the mitotic index, can be eliminated by use of CGH. It is particularly important in the diagnosis of leukemias, and CGH could be a useful tool enabling more precise cytogenetic analysis of leukemic cells. A group of 89 children with acute lymphoblastic leukemia was studied by means of CGH using bone marrow obtained from all consecutive pediatric patients. CGH experiments were performed according to the manufacturer's instruction with minor modifications. In addition, each sample was examined with standard GTG technique and fluorescence in situ hybridization. The conventional cytogenetics failed in 12 patients (13.5%), and 22 patients (24.7%) had a normal karyotype. Structural and numerical changes were found in 55 cases (61.8%) displaying a different abnormalities including deletions, trisomies, tetrasomies, isochromosomes, and markers with unknown origin. However, all samples were successfully analyzed by CGH. We have shown that high-resolution comparative genomic hybridization analysis is a reliable and relatively quick one-step method to identify main aberrations that would not be detected by either conventional G banding or by conventional fluorescence in situ hybridization. It should be considered to establish CGH as a routine analysis for screening patients with acute lymphoblastic leukemia.