Justifiability of amniocentesis on the basis of positive findings of triple test, ultrasound scan and advanced maternal age

Objective. To assess the effectiveness of antenatal screening for chromosomal abnormalities based on maternal age (≥35 years), positive ultrasound findings or a positive triple test. Materials and methods. Retrospective six-year study. The pregnant women routinely underwent established clinical and laboratory practice at the Department of Medical Genetics between 1997 and 2003. The women's case notes were examined to identify indications for karyotyping, gestation period and the outcome of karyotyping and pregnancy. Results. Invasive antenatal tests were performed on 1440 cases, 1168 (81.11%) age 35(a), 72 (5.00%) positive triple test (b), 24 (1.67%) positive ultrasound scanning (c) and 176 (12.2%) other (psychological, personal reasons, etc) (d). The overall positive predictive value was 1.67% (1.6%(a), 1.4% (b), 12.5% (c), 0.0% (d). The constructed model of logistic regression gave an odds-ratio of 8.647 for the "positive ultrasound result vs. maternal age ≥35" indication, while the odds-ratio for the triple test vs. maternal age ≥35 was 0.854. Conclusions. Amniocentesis and cytogenetic analysis of foetal karyotype should be presented as a diagnostic possibility to all women over 35 years. The application of biochemical markers was far from the expected results. If we compare results for indication positive ultrasound scanning vs. maternal age, an oddsratio of ~9 was obtained. These results demonstrate that the likelihood of obtaining positive results (i.e. the presence of chromosome alterations) from an amniocentesis having this indication is almost 9 times higher than from having an amniocentesis performed solely for advanced maternal age

Wider Action Plan and Multidisciplinar Approach Could Be a Wining Idea in Creation of Friendly Environment

Herein, we proposed planning of wide transdisciplinary actions, which bring a solution for economic activity such as transportation, strongly related to pollution output with possible repercussions on climate change and public health. To solve logistics problem by introduction of common intermodal policy, and creation of more friendly transport solution, it is possible to obtain sustainable development, climate change prevention, government policy, and regulation which are all related to human health and creation of health-supportive environment. This approach permits environmental and biological monitoring same as economic results measurement by key performance indicators. This approach implementing emerging scientific knowledge in environmental health science such as genetic epidemiology aimed at understanding how genomic variation impacts phenotypic expression and how genes interact with the environment at the population level with subsequent translation into practical information for clinicians as well as for public health policy creation

Familly with two different cases of post- and pre-natal L1 syndrome; When hydrocephaly become "multidisciplinary headache"

open11openBukvic, Nenad; Boaretto, Francesca; Loverro, Giuseppe; Susca, Francesco C.; Lovaglio, Rosaura; Patruno, Margherita; Bukvic, Dragoslav; Starcevic, Srdjan; Vazza, Giovanni; Mostaciuollo, Maria Luisa; Resta, NicolettaBukvic, Nenad; Boaretto, Francesca; Loverro, Giuseppe; Susca, Francesco C.; Lovaglio, Rosaura; Patruno, Margherita; Bukvic, Dragoslav; Starcevic, Srdjan; Vazza, Giovanni; Mostaciuollo, Maria Luisa; Resta, Nicolett

An integration into the diagnostic workflow in a pediatric patient suspected of having Marfan syndrome

Abstract Background The genetic approach to Marfan syndrome (MFS) has evolved over the last few decades, as has our understanding of the variants' potential structural and functional consequences. It has been proposed that next-generation sequencing be used to improve genetic diagnosis and patient management. To this end, we used a targeted NGS custom panel to perform genetic analysis in a patient with MFS and his or her family members. Case presentation Here, we describe a novel germ-line heterozygous missense variant (transversion c.5371 T > A) found in exon 43 of the FBN1 gene of a patient (proband) with MFS. FBN1 (ENSG0000166147) and TGFB2 (ENSG0000166147) were included in a targeted sequencing panel for MFS (ENSG0000163513). This new variant c.5371 T > A was identified only in the proband, not in unaffected family members or healthy controls. Conclusions Given the massive amount of data generated by gene panel analysis, clinical interpretation of genetic variants may become more difficult. As a result, 3D modeling and multidisciplinary approaches should be used in the analysis and annotation of observed variants. The analysis of the protein's conformational structure in relation to the identified variant could provide useful information. These data can be used to classify observed variants (pathogenic vs non-pathogenic) linked to the MFS phenotype, as well as to track disease progression and potential target treatments

Contraccettivi estro-progestinici: valutazione degli effetti genotosici in vitro

Dottorato di ricerca in biologia della riproduzione umana e animale. 8. cicloConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

What Have We Learned from Patients Who Have Arboleda-Tham Syndrome Due to a De Novo KAT6A Pathogenic Variant with Impaired Histone Acetyltransferase Function? A Precise Clinical Description May Be Critical for Genetic Testing Approach and Final Diagnosis

: Pathogenic variants in genes are involved in histone acetylation and deacetylation resulting in congenital anomalies, with most patients displaying a neurodevelopmental disorder and dysmorphism. Arboleda-Tham syndrome caused by pathogenic variants in KAT6A (Lysine Acetyltransferase 6A; OMIM 601408) has been recently described as a new neurodevelopmental disorder. Herein, we describe a patient characterized by complex phenotype subsequently diagnosed using the clinical exome sequencing (CES) with Arboleda-Tham syndrome (ARTHS; OMIM 616268). The analysis revealed the presence of de novo pathogenic variant in KAT6A gene, a nucleotide c.3385C>T substitution that introduces a premature termination codon (p.Arg1129*). The need for straight multidisciplinary collaboration and accurate clinical description findings (bowel obstruction/megacolon/intestinal malrotation) was emphasized, together with the utility of CES in establishing an etiological basis in clinical and genetical heterogeneous conditions. Therefore, considering the phenotypic characteristics, the condition's rarity and the reviewed literature, we propose additional diagnostic criteria that could help in the development of future clinical diagnostic guidelines. This was possible thanks to objective examinations performed during the long follow-up period, which permitted scrupulous registration of phenotypic changes over time to further assess this rare disorder. Finally, given that different genetic syndromes are associated with distinct genomic DNA methylation patterns used for diagnostic testing and/or as biomarker of disease, a specific episignature for ARTHS has been identified

In Silico Analysis of Possible Interaction between Host Genomic Transcription Factors (TFs) and Zika Virus (ZikaSPH2015) Strain with Combinatorial Gene Regulation; Virus Versus Host—The Game Reloaded

In silico analysis is a promising approach for understanding biological events in complex diseases. Herein we report on the innovative computational workflow allowed to highlight new direct interactions between human transcription factors (TFs) and an entire genome of virus ZikaSPH2015 strain in order to identify the occurrence of specific motifs on a genomic Zika Virus sequence that is able to bind and, therefore, sequester host’s TFs. The analysis pipeline was performed using different bioinformatics tools available online (free of charge). According to obtained results of this in silico analysis, it is possible to hypothesize that these TFs binding motifs might be able to explain the complex and heterogeneous phenotype presentation in Zika-virus-affected fetuses/newborns, as well as the less severe condition in adults. Moreover, the proposed in silico protocol identified thirty-three different TFs identical to the distribution of TFBSs (Transcription Factor Binding Sites) on ZikaSPH2015 strain, potentially able to influence genes and pathways with biological functions confirming that this approach could find potential answers on disease pathogenesis