Detection of Single-Nucleotide and Copy Number Defects Underlying Hyperphenylalaninemia by Next-Generation Sequencing.

Hyperphenylalaninemia (HPA) is the most common inherited amino acid metabolism disorder characterized by serious clinical manifestations, including irreversible brain damage, intellectual deficiency and epilepsy. Due to its extensive genic and allelic heterogeneity, next-generation sequencing (NGS) technology may help to identify the molecular basis of this genetic disease. Herein, we describe the development and validation of a targeted NGS (tNGS) approach for the simultaneous detection of single-nucleotide changes and copy number variations (CNVs) in genes associated with HPA (, , , , , ) or useful for its differential diagnosis ().

The Utility of Genomic Testing for Hyperphenylalaninemia.

Hyperphenylalaninemia (HPA), the most common amino acid metabolism disorder, is caused by defects in enzymes involved in phenylalanine metabolism, with the consequent accumulation of phenylalanine and its secondary metabolites in body fluids and tissues. Clinical manifestations of HPA include mental retardation, and its early diagnosis with timely treatment can improve the prognosis of affected patients. Due to the genetic complexity and heterogeneity of HPA, high-throughput molecular technologies, such as next-generation sequencing (NGS), are becoming indispensable tools to fully characterize the etiology, helping clinicians to promptly identify the exact patients' genotype and determine the appropriate treatment.

Specific alterations of the microRNA transcriptome and global network structure in colorectal cancer after treatment with MAPK/ERK inhibitors.

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has a master control role in various cancer-related biological processes as cell growth, proliferation, differentiation, migration, and apoptosis. It also regulates many transcription factors that control microRNAs (miRNAs) and their biosynthetic machinery. To investigate on the still poorly characterised global involvement of miRNAs within the pathway, we profiled the expression of 745 miRNAs in three colorectal cancer (CRC) cell lines after blocking the pathway with three different inhibitors.

Drug target identification for neuronal apoptosis through a genome scale screening.

During normal nervous system development, physiologically appropriate neuronal apoptosis contributes to a sculpting process that removes approximately one-half of all neurons born during neurogenesis. However, neuronal apoptosis subsequent to this developmental window is physiologically inappropriate for most systems and can contribute to neurodegenerative diseases. Neuronal apoptosis is characterized by specific morphological events and requires the activation of an intrinsic transcriptional program.

Intravenous immune globulin usage for neurological and neuromuscular disorders: an academic centre, 4 years experience.

Intravenous immune globulin (IVIg) use for labeled and unlabeled indications has grown in the last years. Aim of this study was to evaluate the IVIg usage profile for neurological inpatients in a single academic medical centre, over a long period of time. We retrospectively reviewed all approved IVIg transfusions for neurological disorders at Careggi Hospital from 2003 to 2006.