The seroprevalence of the hepatitis B virus in Italian medical students after 3 decades since the introduction of universal vaccination.

Objectives: Since 1991 hepatitis B vaccination has been mandatory for all newborns in Italy. The aim of the study was to verify the long-term seroprevalence and the efficacy of hepatitis B vaccination in medical students of the University of Siena.

Material And Methods: A cross-sectional observational study was conducted on a population of 850 medical students of the University of Siena (322 males and 528 females, mean age: 23 years) by obtaining from the medical reports the serological analysis data for the total anti-hepatitis B antibodies (HBsAb) and information on hepatitis B vaccination (number of vaccine doses, age at the first vaccination, time since the final vaccination dose, country of origin).

TM9SF4 expression in tumor tissues: a novel diagnostic biomarker for gastrointestinal tumors.

Background: The identification of novel biomarkers for the early detection and monitoring of gastric (GC) and colorectal cancer (CRC) is of paramount importance. TM9SF4 is a newly described V-ATPase interacting protein involved in the malignant progression of cancer cells. While TM9SF4 expression pattern and cellular localization have been described in in tumor cell lines of different histotypes, its expression in gastrointestinal tumor tissues has never been investigated.

Isolation of extracellular vesicles improves the detection of mutant DNA from plasma of metastatic melanoma patients.

Detection of BRAF within cell free tumor DNA (ctDNA) is emerging as a promising means to improve patients' stratification or enable BRAF inhibitor (BRAFi) therapeutic monitoring in a minimally invasive manner. Here, we investigated whether extracellular vesicle-(EV)-associated-DNA (EV-DNA) has value as an alternative source of circulating BRAF. To do so, we identified a clinical practice-compatible protocol for the isolation of EV-DNA and assessed BRAF gene status on plasma samples from metastatic melanoma patients at the beginning and during BRAFi therapy.

When Less Is More: Specific Capture and Analysis of Tumor Exosomes in Plasma Increases the Sensitivity of Liquid Biopsy for Comprehensive Detection of Multiple Androgen Receptor Phenotypes in Advanced Prostate Cancer Patients.

We evaluated the advantages and the reliability of novel protocols for the enrichment of tumor extracellular vesicles (EVs), enabling a blood-based test for the noninvasive parallel profiling of multiple androgen receptor ( gene alterations. Three clinically relevant variants related to response/resistance to standard-of-care treatments (-V7 transcript, T878A point mutation and gene amplification) were evaluated by digital PCR in 15 samples from patients affected by Castration-Resistant Prostate Cancer (CRPC). Plasma was processed to obtain circulating RNA and DNA using protocols based on tumor EVs enrichment through immuno-affinity and peptide-affinity compared to generic extraction kits.

iPSC-derived neurons profiling reveals GABAergic circuit disruption and acetylated α-tubulin defect which improves after iHDAC6 treatment in Rett syndrome.

Mutations in MECP2 gene have been identified in more than 95% of patients with classic Rett syndrome, one of the most common neurodevelopmental disorders in females. Taking advantage of the breakthrough technology of genetic reprogramming, we investigated transcriptome changes in neurons differentiated from induced Pluripotent Stem Cells (iPSCs) derived from patients with different mutations. Profiling by RNA-seq in terminally differentiated neurons revealed a prominent GABAergic circuit disruption along with a perturbation of cytoskeleton dynamics.

Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh gene.

We report here the case of a young male who started to show verbal fluency disturbance, clumsiness and gait anomalies at the age of 3.5years and presented bilateral striatal necrosis. Clinically, the diagnosis was compatible with Leigh syndrome but the underlying molecular defect remained elusive even after exome analysis using autosomal/X-linked recessive or de novo models.

Combined ultrasound and exome sequencing approach recognizes Opitz G/BBB syndrome in two malformed fetuses.

Orofacial clefts are the most common congenital craniofacial anomalies and can occur as an isolated defect or be associated with other anomalies such as posterior fossa anomalies as a part of several genetic syndromes. We report two consecutive voluntary pregnancy interruptions in a nonconsanguineous couple following the fetal ultrasound finding of cleft lip and palate and posterior fossa anomalies confirmed by means of post-termination examination on the second fetus. The quantitative fluorescent PCR, the karyotype, and the comparative genomic hybridization-array analysis after amniocentesis were normal.

Exploiting the potential of next-generation sequencing in genomic medicine.

Introduction: The review highlights the impact of next-generation sequencing (NGS) on genomic medicine and the consequences of the progression from a single-gene panel technology to a whole exome sequencing approach.

Areas Covered: We brought together literature-based evidences, personal unpublished data and clinical experience to provide a critical overview of the impact of NGS on our daily clinical practice. Expert commentary: NGS has changed the role of clinical geneticist and has broadened the view accomplishing a transition from a monogenic Mendelian perspective to an oligogenic approach to disorders.

Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress.

We highlight the importance of exome sequencing in solving a clinical case of a child who died at 14 months after a series of respiratory crises. He was the half-brother of a girl diagnosed at 7 years with the early-onset seizure variant of Rett syndrome due to CDKL5 mutation. We performed a test for CDKL5 in the boy, which came back negative.

Exome sequencing analysis in a pair of monozygotic twins re-evaluates the genetics behind their intellectual disability and reveals a CHD2 mutation.

Background: Neurodevelopmental disorders include a broad spectrum of conditions, which are characterized by delayed motor and/or cognitive milestones and by a variable range of intellectual disability with or without an autistic behavior. Several genetic factors have been implicated in intellectual disability onset and exome sequencing studies have recently identified new inherited or de novo mutations in patients with neurodevelopmental disorders.

Case: We report the case of two monozygotic twins who came for the first time to our attention at the age of 20months for a global neurodevelopmental delay associated with an autism spectrum disorder, hypotonia, postnatal microcephaly, stereotypic movements and circadian rhythm alterations in association with late-onset epilepsy.

MECP2 missense mutations outside the canonical MBD and TRD domains in males with intellectual disability.

Methyl-CpG-binding protein 2 (MeCP2) is a nuclear protein highly expressed in neurons that is involved in transcriptional modulation and chromatin remodeling. Mutations in MECP2 in females are associated with Rett syndrome, a neurological disorder characterized by a normal neonatal period, followed by the arrest of development and regression of acquired skills. Although it was initially thought that MECP2 pathogenic mutations in males were not compatible with life, starting from 1999 about 60 male patients have been identified and their phenotype varies from severe neonatal encephalopathy to mild intellectual disability.

Revealing the complexity of a monogenic disease: rett syndrome exome sequencing.

Rett syndrome (OMIM#312750) is a monogenic disorder that may manifest as a large variety of phenotypes ranging from very severe to mild disease. Since there is a weak correlation between the mutation type in the Xq28 disease-gene MECP2/X-inactivation status and phenotypic variability, we used this disease as a model to unveil the complex nature of a monogenic disorder. Whole exome sequencing was used to analyze the functional portion of the genome of two pairs of sisters with Rett syndrome.