Combined biochemical profiling and DNA sequencing in the expanded newborn screening for inherited metabolic diseases: the experience in an Italian reference center.

Background: Newborn screening (NBS) programs have significantly improved the health and outcomes of patients with inherited metabolic disorders (IMDs). Methods based on liquid chromatography/mass spectrometry (LC-MS/MS) analysis are viewed worldwide as the gold standard procedure for the expanded NBS programs for these disorders. Advanced molecular technologies point to genomic sequencing as an alternative and feasible strategy for the screening of genetic diseases, including IMDs.

Multi-Omics Study Reveals Nc886/vtRNA2-1 as a Positive Regulator of Prostate Cancer Cell Immunity.

Noncoding RNA 886 has emerged as a pivotal regulatory RNA with distinct functions across tissues, acting as a regulator of protein activity by directly binding to protein partners. While it is well recognized as a tumor suppressor in prostate cancer, the underlying molecular mechanisms remain elusive. To discover the principal pathways regulated by nc886 in prostate cancer, we used a transcriptomic and proteomic approach analyzing malignant DU145, LNCaP, PC3, and benign RWPE-1 prostate cell line models transiently transfected with in vitro transcribed nc886 or antisense oligonucleotides.

A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.

Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe a case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment.

Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation.

Extracellular DNA (exDNA) can be actively released by living cells and different putative functions have been attributed to it. Further, homologous exDNA has been reported to exert species-specific inhibitory effects on several organisms. Here, we demonstrate by different experimental evidence, including H-NMR metabolomic fingerprint, that the growth rate decline in fed-batch cultures is determined by the accumulation of exDNA in the medium.

Integrated exome and transcriptome analysis prioritizes MAP4K4 de novo frameshift variants in autism spectrum disorder as a novel disease-gene association.

The application of next-generation sequencing (NGS) to clinical practice is still hampered by the ability to interpret the clinical relevance of novel variants and the difficulty of evaluating their effect in specific tissues. Here, we applied integrated genomic approaches for interrogating blood samples of two unrelated individuals with neurodevelopmental disorders and identified a novel neuro-pathogenic role for the Mitogen-Activated Protein Kinase 4 gene (MAP4K4). In particular, we identified two novel frameshift variants in coding exons expressed in the blood and neuronal isoforms.