Posts By: Nicola Brunetti-Pierri

Disease modeling with iPS cell and heart-on-chip technologies

Posted by & filed under Tools.

The study by Wang et al combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) and tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome, a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ). Using Barth syndrome iPSC-derived cardiomyocytes (iPSC-CMs), they defined metabolic, structural and functional abnormalities associated with TAZ mutation. Barth syndrome […]

Neu-Laxova syndrome is an inborn error of serine biosynthesis

Posted by & filed under Part 08: AMINO ACIDS.

Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by severe fetal growth restriction, microcephaly, a distinct facial appearance, ichthyosis, skeletal anomalies, and perinatal lethality. Through a positional-mapping study combining autozygosity mapping and whole-exome sequencing, Shaheen and colleagues surprisingly found that NLS is caused by mutations in PHGDH encoding for 3-phosphoglycerate dehydrogenase is the first enzyme in the […]

Maternally inherited mutations in CADPS2: a novel cause for intellectual disability and autism spectrum disorders

Posted by & filed under Part 28: NEUROGENETICS.

Part 28: Neurogenetics Bonora and colleagues have recently identified an intragenic deletion of maternal origin in two siblings with intellectual disability (ID) and epilepsy in the CADPS2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2DR). They next screened 223 additional patients with ID and autism spectrum disorder and identified a […]

Gene editing for HIV therapy

Posted by & filed under Part 02: PERSPECTIVES.

CCR5 is the major co-receptor for human immunodeficiency virus (HIV). The New England Journal of Medicine recently published the results of a clinical trial investigating the safety of the infusion of autologous CD4 T-cells in which the CCR5 gene was rendered permanently dysfunctional by a zinc-finger nuclease (ZFN). Following infusion of genetically edited cells, the CD4 T-cell count increased significantly […]

ADNP mutations cause autism syndrome

Posted by & filed under Part 28: NEUROGENETICS.

Genetic diagnosis of autism spectrum disorders (ASD) can be established in only a minority of patients. Known genetic causes include copy number variants and monogenic defects, such as Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. The large […]

Abnormal signaling triggers cardiomyopathy in mice with Marfan syndrome

Posted by & filed under Part 22: CONNECTIVE TISSUE.

Francesco Ramirez’s group found that abnormal extracellular matrix (ECM) signaling results in dilated cardiomyopathy (DCM) in fibrillin 1–deficient mice. These mice develop enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling. Consistent with abnormal mechanosignaling, normal cardiac size and function […]

A universal biomarker for lysosomal storage disorders

Posted by & filed under Part 16: LYSOSOMAL DISORDERS.

Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births. This study proposes Lysotracker a commercially available fluorescent probe to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. This marker was validated in a mouse model of the LSD Niemann-Pick type C1 disease […]

A novel therapeutic target for Gaucher disease

Posted by & filed under Part 16: LYSOSOMAL DISORDERS.

Gaucher’s disease (GD) due to mutations in the glucocerebrosidase gene (GBA) is divided into three clinical subtypes based on the absence (type 1) or presence (types 2 and 3) of neurological signs.  Glucosylceramide and glucosylsphingosine accumulation in the brain leads to massive neuronal loss in patients with neuronopathic GD (nGD). Vitner and colleagues found that modulating the receptor-interacting […]

Lysosomal enzyme protects against arthritis

Posted by & filed under Part 16: LYSOSOMAL DISORDERS.

A recent work in the Journal of Clinical Investigation highlights the role of lysosomal enzymes for protection against arthritis. Lysosomal enzyme beta-glucuronidase (GUSB) was found as a key regulator of arthritis severity associated to Lyme disease that is caused by the spirochete Borrelia burgdorferi, the most prevalent arthropod-borne illness in the United States. Severely arthritic C3H […]

A novel inborn error of coenzyme A biosynthesis implicated in neurodegeneration with brain iron accumulation (NBIA)

Posted by & filed under New IEM.

Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. So far, the identified defects responsible for NBIA include: 1. pantothenate kinase-associated neurodegeneration (PKAN) due to mutations in PANK2; 2. phospholipase A2-associated neurodegeneration (PLAN) due to mutations […]