Maternally derived 15q11.2-q13.1 duplication and H19-DMR hypomethylation in a patient with Silver?Russell syndrome

Silver?Russell syndrome (SRS) is a congenital developmental disorder characterized by intrauterine and postnatal growth failure, craniofacial features (including a triangular shaped face and broad forehead), relative macrocephaly, protruding forehead, body asymmetry and feeding difficulties. Hypomethylation of the H19 differentially methylated region (DMR) on chromosome 11p15.5 is the most common cause of the SRS phenotype. We report the first SRS patient with hypomethylation of the H19-DMR and maternally derived 15q11.2-q13.1 duplication. Although her clinical manifestations overlapped with those of previously reported SRS cases, the patient’s intellectual disability and facial dysmorphic features were inconsistent with the SRS phenotype. Methylation analyses, array comparative genomic hybridization, and a FISH analysis revealed the hypomethylation of the H19-DMR and a maternally derived interstitial 5.7?Mb duplication at 15q11.2-q13.1 encompassing the Prader?Willi/Angelman critical region in the patient. On the basis of the genetic and clinical findings in the present and previously reported cases, it is unlikely that the 15q duplication in the patient led to the development of hypomethylation of the H19-DMR and it is reasonable to consider that the characteristic phenotype in the patient was caused by the coexistence of the two (epi)genetic conditions. Further studies are needed to clarify the mechanisms leading to methylation aberrations in SRS

Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

Nouran B AbdAllah,1 Essam Al Ageeli,2 Abdullah Shbeer,3 Jawaher A Abdulhakim,4 Eman A Toraih,5,6 Doaa O Salman,6 Manal S Fawzy,7,8 Sanaa S Nassar1 1Department of Pediatrics, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 2Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 3Anesthesiology and Intensive Care, Department of Surgery, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 4Medical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia; 5Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA; 6Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 7Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 8Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi ArabiaCorrespondence: Manal S Fawzy, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, Email [email protected] Eman A Toraih, Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA, Email [email protected]: Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarkers for sepsis. We aimed to profile the expression signature of three inflammation-related lncRNAs, MALAT1, ANRIL, and HHOTAIR, in the plasma of neonates with sepsis and correlate these signatures with the phenotype.Patients and Methods: This case–control study included 124 neonates with sepsis (88 survivors/36 non-survivors) admitted to the neonatal ICU and 17 healthy neonates. The relative expressions were quantified by real-time PCR and correlated to the clinic-laboratory data.Results: The three circulating lncRNAs were upregulated in the cases; the median levels were MALAT1 (median = 1.71, IQR: − 0.5 to 3.27), ANRIL (median = 1.09, IQR: 0.89 to 1.30), and HOTAIR (median = 1.83, IQR: 1.44 to 2.41). Co-expression analysis showed that the three studied lncRNAs were directly correlated (all p-values < 0.001). Overall and stratification by sex analyses revealed significantly higher levels of the three lncRNAs in non-survivors compared to the survivor group (all p-values < 0.001). Principal component analysis showed a clear demarcation between the two study cohorts in males and females. Cohorts with upregulated ANRIL (hazard ratio; HR = 4.21, 95% CI = 1.15– 10.4, p=0.030) and HOTAIR (HR = 2.49, 95% CI = 1.02– 6.05, p=0.044) were at a higher risk of mortality.Conclusion: Circulatory MALAT1, ANRIL, and HOTAIR were upregulated in neonatal sepsis, and the latter two may have the potential as prognostic biomarkers for survival in neonatal sepsis.Keywords: neonatal sepsis, long non-coding RNAs, MALAT1, ANRIL, HOTAIR, surviva

Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography

Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, weight, hypertension, and MALAT1 (T &gt; C) (negative correlation), explained the variance between patients/control groups via a principal component analysis. Incorporating the principal components into a logistic regression model to predict CAD yielded a 0.92 AUC. In conclusion: MIAT rs1061540 and MALAT1 rs3200401 variants were associated with CAD severity and Gensini score in the present sample of the Egyptian population. Further large multi-center and functional analyses are needed to confirm the results and identify the underlying molecular mechanisms

Marginal Adaptation and Internal Fit of 3D-Printed Provisional Crowns and Fixed Dental Prosthesis Resins Compared to CAD/CAM-Milled and Conventional Provisional Resins: A Systematic Review and Meta-Analysis

The aim of this systematic review was to evaluate the marginal fit and internal adaptation of provisional crowns and fixed dental prostheses (FDPs) fabricated using 3D-printing resins and compared them with those fabricated by CAD/CAM (computer-aided designing/computer-aided manufacturing) milling and conventional resins. The null hypotheses tested were that there would be no differences in the marginal fit and internal adaptation of 3D-printed provisional crowns and FDP resins when compared to CAD/CAM-milled and conventional provisional resins. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to construct this systematic review. The focused PICO/PECO (Population, Intervention/Exposure, Comparison, Outcome) question was &ldquo;Do provisional crowns and FDPs (P) fabricated by 3D-printing (I) have similar marginal adaptation and internal fit (O) when compared to those fabricated by CAD/CAM milling and conventional techniques (C)?&rdquo;. The protocol used for this systematic review was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO). Electronic databases (e.g., MEDLINE/PubMed and Web of Science (Core Collection)) were systematically searched for indexed English literature published up to June 2022. In the initial electronic search of the selected databases, 519 articles were identified. Duplicates were removed, and screening was performed to select the articles that met the preset inclusion criteria. Sixteen studies were selected for qualitative analysis, but only ten of them provided comparative data and were selected for quantitative analysis. The modified CONSORT scale was used for qualitative analysis, and most of the included studies were rated to be of moderate quality. Based on the findings, it could be concluded that provisional crowns and FDPs fabricated from 3D-printing resins have a superior marginal fit and internal adaptation when compared to CAD/CAM-milled and conventional provisional resins; thus, they can be used as a dependable alternative to other resins

Myhre and LAPS syndromes: Clinical and molecular review of 32 patients

Myhre syndrome is characterized by short stature, brachydactyly, facial features, pseudomuscular hypertrophy, joint limitation and hearing loss. We identified SMAD4 mutations as the cause of Myhre syndrome. SMAD4 mutations have also been identified in laryngotracheal stenosis, arthropathy, prognathism and short stature syndrome (LAPS). This study aimed to review the features of Myhre and LAPS patients to define the clinical spectrum of SMAD4 mutations. We included 17 females and 15 males ranging in age from 8 to 48 years. Thirty were diagnosed with Myhre syndrome and two with LAPS. SMAD4 coding sequence was analyzed by Sanger sequencing. Clinical and radiological features were collected from a questionnaire completed by the referring physicians. All patients displayed a typical facial gestalt, thickened skin, joint limitation and muscular pseudohypertrophy. Growth retardation was common (68.7%) and was variable in severity (from -5.5 to -2 SD), as was mild-to-moderate intellectual deficiency (87.5%) with additional behavioral problems in 56.2% of the patients. Significant health concerns like obesity, arterial hypertension, bronchopulmonary insufficiency, laryngotracheal stenosis, pericarditis and early death occurred in four. Twenty-nine patients had a de novo heterozygous SMAD4 mutation, including both patients with LAPS. In 27 cases mutation affected Ile500 and in two cases Arg496. The three patients without SMAD4 mutations had typical findings of Myhre syndrome. Myhre-LAPS syndrome is a clinically homogenous condition with life threatening complications in the course of the disease. Our identification of SMAD4 mutations in 29/32 cases confirms that SMAD4 is the major gene responsible for Myhre syndrome