Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve split-hand/foot malformation type 3.

Split-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigate the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice.

Impact of Different Measures of Body Size on the Radiation Dose During Coronary Angiography and Percutaneous Coronary Intervention: Results from a Large Single Center Cohort.

Efforts to reduce and optimize the radiation exposure during coronary angiography and intervention have pointed at patients' body size as a major determinant of irradiation for the patients and operators. We aimed at comparing body weight and body mass index (BMI) among consecutive patients undergoing angiographic procedures (coronary angiography and/or interventions) in a single center. Patients were divided in normal weight (NW, BMI <25 Kg/m) and overweight (OW, BMI ≥25 Kg/m).

A Golden Ten: A Decade of Open Access Society Publishing.

Shining On! Happy first 10 years, ChemistryOpen! From little more than a new trend in chemistry publishing, the Open Access model has grown into a major theme in publishing in the last decade. The idea of Open Science has become instrumental for the collaboration among scientists, not only during the pandemic, and ChemistryOpen is ready to start its next decade in a much more open world!

Electroclinical features of MEF2C haploinsufficiency-related epilepsy: A multicenter European study.

Purpose: Epilepsy is a main manifestation in the autosomal dominant mental retardation syndrome caused by heterozygous variants in MEF2C. We aimed to delineate the electro-clinical features and refine the genotype-phenotype correlations in patients with MEF2C haploinsufficiency.

Methods: We thoroughly investigated 25 patients with genetically confirmed MEF2C-syndrome across 12 different European Genetics and Epilepsy Centers, focusing on the epileptic phenotype.

Detailed Clinical and Psychological Phenotype of the X-linked -Related Neurodevelopmental Disorder.

Objective: To expand the clinical phenotype of the X-linked -related neurodevelopmental disorder in 33 individuals.

Methods: Participants were diagnosed with pathogenic or likely pathogenic variants in using American College of Medical Genetics and Genomics/Association of Molecular Pathology criteria, largely identified via clinical exome sequencing. Genetic reports were reviewed.

10 Years of Open Access Society Publishing.

That was ten, this is now! The Editor-in-Chief of ChemistryOpen Francesca Novara discusses what 2020 meant for the development of open science and ChemistryOpen and what is the landscape in which ChemistryOpen will celebrate its 10th anniversary.

The FAST-STEMI Network in Biella From 2013 to 2019: Impact of the Delocalization of the Hospital Facilities on Ischemia Time and In-hospital Outcomes.

Background: The optimization of the strategies for myocardial revascularization has improved the outcomes of patients with ST-segment elevation myocardial infarction. In Piedmont, the FAST-STEMI regional network was created for improving the management and transportation of ST-segment elevation (STEMI) patients to primary percutaneous coronary intervention facilities, reducing the time to reperfusion. Within this network, the Hospital of Biella was delocalized in December 2014 to a new suburban structure designed for an easier access, which might have shortened the duration of patients' transportation and ischemia, with potential positive prognostic effects.

The Search for Molecular Markers in a Gene-Orphan Case Study of a Pediatric Spinal Cord Pilocytic Astrocytoma.

Background/aim: We herein presented a case of pediatric spinal cord pilocytic astrocytoma diagnosed on the basis of histopathological and clinical findings.

Materials And Methods: Given the paucity of data on genetic features for this tumor, we performed exome, array CGH and RNA sequencing analysis from nucleic acids isolated from a unique and not repeatable very small amount of a formalin-fixed, paraffin-embedded (FFPE) specimen.

Results: DNA mutation analysis, comparing tumor and normal lymphocyte peripheral DNA, evidenced few tumor-specific single nucleotide variants in DEFB119, MUC5B, NUDT1, LTBP3 and CPSF3L genes.

A Big Year for Open Access Chemistry Publishing.

! The new Editor-in-Chief of Francesca Novara looks back on her first year with the journal and discusses the increasingly strong position of in a developing open access world.

Missense variants in the Arg206 residue of HNRNPH2: Further evidence of causality and expansion of the phenotype.

Missense variants in HNRNPH2 cause Bain type syndromic X-linked intellectual disability (XLID). To date, only six affected females and three affected males have been reported in the literature, and the phenotype has yet to be delineated in detail. Here, we report on a 35-year-old female with a novel de novo variant in HNRNPH2, providing further evidence that missense changes in the nuclear localization sequence cause Bain type XLID and that aminoacid 206 likely represents a mutational hotspot.

De novo unbalanced translocations have a complex history/aetiology.

We investigated 52 cases of de novo unbalanced translocations, consisting in a terminally deleted or inverted-duplicated deleted (inv-dup del) 46th chromosome to which the distal portion of another chromosome or its opposite end was transposed. Array CGH, whole-genome sequencing, qPCR, FISH, and trio genotyping were applied. A biparental origin of the deletion and duplication was detected in 6 cases, whereas in 46, both imbalances have the same parental origin.

The Nobel Legacy: A Journey through Chemistry Inspired by the Achievements of Nobel Laureates.

The Prize is right! Chemistry-A European Journal will start an exciting journey exploring the significance of Nobel Prize awards in Chemistry in the corresponding contemporary chemistry fields. In this new journal feature called "The Nobel Legacy", a recurring series of invited Review-type articles each one connected to a particular Nobel Prize in Chemistry will be published.

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations.

Birth defects that involve the cerebral cortex - also known as malformations of cortical development (MCD) - are important causes of intellectual disability and account for 20-40% of drug-resistant epilepsy in childhood. High-resolution brain imaging has facilitated in vivo identification of a large group of MCD phenotypes. Despite the advances in brain imaging, genomic analysis and generation of animal models, a straightforward workflow to systematically prioritize candidate genes and to test functional effects of putative mutations is missing.

Three Reportedly Unrelated Families With Liddle Syndrome Inherited From a Common Ancestor.

Liddle syndrome is considered a rare Mendelian hypertension. We have previously described 3 reportedly unrelated families, native of an Italian area around the Strait of Messina, carrying the same mutation (βP617L) of the epithelial sodium channel. The aims of our study were (1) to evaluate whether a close genomic relationship exists between the 3 families through the analysis of mitochondrial DNA and Y chromosome; and (2) to quantify the genomic relatedness between the patients with Liddle syndrome belonging to the 3 families and assess the hypothesis of a mutation shared through identity by descent.

Diagnostic application of a capture based NGS test for the concurrent detection of variants in sequence and copy number as well as LOH.

Whole exome sequencing (WES) has made the identification of causative SNVs/InDels associated with rare Mendelian conditions increasingly accessible. Incorporation of softwares allowing CNVs detection into the WES bioinformatics pipelines may increase the diagnostic yield. However, no standard protocols for this analysis are so far available and CNVs in non-coding regions are totally missed by WES, in spite of their possible role in the regulation of the flanking genes expression.

Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG and 16q24.3 microdeletion syndromes: 12 new cases.

16q24 deletion involving the ANKRD11 gene, ranging from 137 kb to 2 Mb, have been associated with a microdeletion syndrome characterized by variable cognitive impairment, autism spectrum disorder, facial dysmorphisms with dental anomalies, brain abnormalities essentially affecting the corpus callosum and short stature. On the other hand, patients carrying either deletions encompassing solely ANKRD11 or its loss-of-function variants were reported in association with the KBG syndrome, characterized by a very similar phenotype, including mild-to-moderate intellectual disability, short stature and macrodontia of upper incisors, with inter and intrafamilial variability. To assess whether the haploinsufficiency of ANKRD11-flanking genes, such as ZFPM1, CDH15 and ZNF778, contributed to either the severity of the neurological impairment or was associated with other clinical features, we collected 12 new cases with a 16q24.

Guideline recommendations for diagnosis and clinical management of Ring14 syndrome-first report of an ad hoc task force.

Background: Ring chromosome 14 syndrome is a rare chromosomal disorder characterized by early onset refractory epilepsy, intellectual disability, autism spectrum disorder and a number of diverse health issues.

Results: The aim of this work is to provide recommendations for the diagnosis and management of persons affected by ring chromosome 14 syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years subjects affected by ring chromosome 14 syndrome. The literature search was performed in 2016.

Developmental trends of communicative skills in children with chromosome 14 aberrations.

Unlabelled: Children with chromosome 14 aberrations usually show developmental delays, intellectual disability, neurological disorders and behaviour problems. The aim of the present study is to describe the developmental trajectories of the communicative skills of children with chromosome 14 aberrations, considering the possible relationships between the patterns of language development and the children's clinical characteristics (e.g.

Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan-Herndon-Dudley Syndrome.

Mutations in the thyroid hormone transporter SLC16A2 (MCT8) cause the Allan-Herndon-Dudley Syndrome (AHDS), characterized by severe psychomotor retardation and peripheral thyrotoxicosis. Here, we report three newly identified AHDS patients. Previously documented mutations were identified in probands 1 (p.

Dissection of partial 21q monosomy in different phenotypes: clinical and molecular characterization of five cases and review of the literature.

Background: Partial deletion of chromosome 21q is a very rare chromosomal abnormality associated with highly variable phenotypes, such as facial dysmorphic features, heart defects, seizures, psychomotor delay, and severe to mild intellectual disability, depending on the location and size of deletions. So far, three broad deletion regions of 21q have been correlated with the clinical phenotype.

Results: We described the clinical and genetic features of three family members (father and two siblings) and other two unrelated patients with very wide range in age of diagnosis.

Scanning electron microscopy analysis of the growth of dental plaque on the surfaces of removable orthodontic aligners after the use of different cleaning methods.

Background: Advances in orthodontics are leading to the use of minimally invasive technologies, such as transparent removable aligners, and are able to meet high demands in terms of performance and esthetics. However, the most correct method of cleaning these appliances, in order to minimize the effects of microbial colonization, remains to be determined.

Purpose: The aim of the present study was to identify the most effective method of cleaning removable orthodontic aligners, analyzing the growth of dental plaque as observed under scanning electron microscopy.

Comprehensive characterization of mesenchymal stromal cells from patients with Fanconi anaemia.

Fanconi anaemia (FA) is an inherited disorder characterized by pancytopenia, congenital malformations and a predisposition to develop malignancies. Alterations in the haematopoietic microenvironment of FA patients have been reported, but little is known regarding the components of their bone marrow (BM) stroma. We characterized mesenchymal stromal cells (MSCs) isolated from BM of 18 FA patients both before and after allogeneic haematopoietic stem cell transplantation (HSCT).

Heterozygous deletion of CHL1 gene: detailed array-CGH and clinical characterization of a new case and review of the literature.

CHL1 gene maps at 3p26.3 and encodes a cell adhesion molecule of the immunoglobulin superfamily highly expressed in the brain. CHL1 regulates neuronal migration and neurite overgrowth in the developing brain, while in mature neurons it accumulates in the axonal membrane and regulates synapse function via the clathrin-dependent pathways.