Oral HPV16 DNA as a screening tool to detect early oropharyngeal squamous cell carcinoma.

Given that oropharyngeal squamous cell carcinoma (OPSCC) have now surpassed cervical cancer as the most common human papillomavirus (HPV)-driven cancer, there is an interest in developing non-invasive predictive biomarkers to early detect HPV-driven OPSCC. In total, 665 cancer-free individuals were recruited from Queensland, Australia. Oral HPV16 DNA positivity in those individuals was determined by our in-house developed sensitive PCR method.

Oral HPV16 Prevalence in Oral Potentially Malignant Disorders and Oral Cavity Cancers.

The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD ( = 83) and OC ( = 106) patients. HPV16 genotype, viral load, physical status (episomal vs.

Mice with megalencephalic leukoencephalopathy with cysts: a developmental angle.

Objective: Megalencephalic leukoencephalopathy with cysts (MLC) is a genetic disease characterized by infantile onset white matter edema and delayed onset neurological deterioration. Loss of MLC1 function causes MLC. MLC1 is involved in ion-water homeostasis, but its exact role is unknown.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: clinical and genetic characterization and target for therapy.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is a disorder caused by recessive mutations in the gene DARS2, which encodes mitochondrial aspartyl-tRNA synthetase. Recent observations indicate that the phenotypic range of the disease is much wider than initially thought. Currently, no treatment is available.

Released selective pressure on a structural domain gives new insights on the functional relaxation of mitochondrial aspartyl-tRNA synthetase.

Mammalian mitochondrial aminoacyl-tRNA synthetases are nuclear-encoded enzymes that are essential for mitochondrial protein synthesis. Due to an endosymbiotic origin of the mitochondria, many of them share structural domains with homologous bacterial enzymes of same specificity. This is also the case for human mitochondrial aspartyl-tRNA synthetase (AspRS) that shares the so-called bacterial insertion domain with bacterial homologs.

A yeast purification system for human translation initiation factors eIF2 and eIF2Bε and their use in the diagnosis of CACH/VWM disease.

Recessive inherited mutations in any of five subunits of the general protein synthesis factor eIF2B are responsible for a white mater neurodegenerative disease with a large clinical spectrum. The classical form is called Childhood Ataxia with CNS hypomyelination (CACH) or Vanishing White Matter Leukoencephalopathy (VWM). eIF2B-related disorders affect glial cells, despite the fact that eIF2B is a ubiquitous protein that functions as a guanine-nucleotide exchange factor (GEF) for its partner protein eIF2 in the translation initiation process in all eukaryotic cells.

Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways.

The autosomal recessive white matter disorder LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is caused by mutations in DARS2, coding for mtAspRS (mitochondrial aspartyl-tRNA synthetase). Generally, patients are compound heterozygous for mutations in DARS2. Many different mutations have been identified in patients, including several missense mutations.

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA.

LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is an autosomal recessive white matter disorder with slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction. Magnetic resonance imaging shows characteristic abnormalities in the cerebral white matter and specific brain stem and spinal cord tracts. LBSL is caused by mutations in the gene DARS2, which encodes mtAspRS (mitochondrial aspartyl-tRNA synthetase).

Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation.

Megalencephalic leucoencephalopathy with subcortical cysts is a genetic brain disorder with onset in early childhood. Affected infants develop macrocephaly within the first year of life, after several years followed by slowly progressive, incapacitating cerebellar ataxia and spasticity. From early on, magnetic resonance imaging shows diffuse signal abnormality and swelling of the cerebral white matter, with evidence of highly increased white matter water content.

Molecular mechanisms of MLC1 and GLIALCAM mutations in megalencephalic leukoencephalopathy with subcortical cysts.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy caused by mutations in MLC1 or GLIALCAM. The GLIALCAM gene product functions as an MLC1 beta-subunit. We aim to further clarify the molecular mechanisms of MLC caused by mutations in MLC1 or GLIALCAM.

Severity of vanishing white matter disease does not correlate with deficits in eIF2B activity or the integrity of eIF2B complexes.

Autosomal recessive mutations in eukaryotic initiation factor 2B (eIF2B) cause leukoencephalopathy vanishing white matter with a wide clinical spectrum. eIF2B comprises five subunits (α-ε; genes EIF2B1, 2, 3, 4 and 5) and is the guanine nucleotide-exchange factor (GEF) for eIF2. It plays a key role in protein synthesis.

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case without elevated white matter lactate.

A 17-year-old Indian boy with gradually progressive ataxia with onset at 12 years of age is described. Magnetic resonance imaging (MRI) of the brain revealed extensive, inhomogeneous signal abnormalities in the cerebral white matter, with involvement of selected tracts in the brain stem and spinal cord. The imaging findings were characteristic of leukoencephalopathy with brain stem and spinal cord involvement and high lactate, a recently described leukodystrophy.

Knockdown of MLC1 in primary astrocytes causes cell vacuolation: a MLC disease cell model.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, in the majority of cases caused by mutations in the MLC1 gene. MRI from MLC patients shows diffuse cerebral white matter signal abnormality and swelling, with evidence of increased water content. Histopathology in a MLC patient shows vacuolation of myelin, which causes the cerebral white matter swelling.

Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene.

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation in the first Polish patient.

Leukoencephalopathy with brain stem and spinal cord involvement and elevated white matter lactate (LBSL) is a very rare autosomal recessive mitochondrial disorder. Clinically patients have slowly progressive ataxia, pyramidal syndrome and dorsal column dysfunction. The disease is defined on the basis of characteristic abnormalities observed on magnetic resonance imaging such as inhomogeneous, spotty involvement of the cerebral white matter, selective involvement of brain stem and spinal cord tracts as well as lactate elevation in the affected white matter on spectroscopy.

Defective glial maturation in vanishing white matter disease.

Vanishing white matter (VWM) disease is a genetic leukoencephalopathy linked to mutations in the eukaryotic translation initiation factor 2B. It is a disease of infants, children, and adults who experience a slowly progressive neurologic deterioration with episodes of rapid clinical worsening triggered by stress and eventually leading to death. Characteristic neuropathologic findings include cystic degeneration of the white matter with scarce reactive gliosis, dysmorphic astrocytes, and paucity of myelin despite an increase in oligodendrocytic density.

A human pathology-related mutation prevents import of an aminoacyl-tRNA synthetase into mitochondria.

Mutations in the nuclear gene coding for the mitochondrial aspartyl-tRNA synthetase, a key enzyme for mitochondrial translation, are correlated with leukoencephalopathy. A Ser⁴⁵ to Gly⁴⁵ mutation is located in the predicted targeting signal of the protein. We demonstrate in the present study, by in vivo and in vitro approaches, that this pathology-related mutation impairs the import process across mitochondrial membranes.

Vanishing white matter disease associated with ptosis and myoclonic seizures.

A 5-year-old boy who presented with progressive ataxia, neuroregression, and worsening with febrile illnesses is described. He also had myoclonic jerks and ptosis. His elder sister had died of a similar illness.

Leukoencephalopathy with vanishing white matter: a review.

Vanishing white matter (VWM) is one of the most prevalent inherited childhood leukoencephalopathies, but this may affect people of all ages, including neonates and adults. It is a progressive disorder clinically dominated by cerebellar ataxia and in which minor stress conditions, such as fever or mild trauma, provoke major episodes of neurologic deterioration. Typical pathological findings include increasing white matter rarefaction and cystic degeneration, oligodendrocytosis with highly characteristic foamy oligodendrocytes, meager astrogliosis with dysmorphic astrocytes, and loss of oligodendrocytes by apoptosis.

Two cases with megalencephalic leukoencephalopathy with subcortical cysts and MLC1 mutations in the Turkish population.

Megalencephalic leukoencephalopathy with subcortical cysts is a rare leukodystrophy that is characterized by macrocephaly and a slowly progressive clinical course. It is one of the most commonly reported leukoencephalopathies in Turkey. Mutations in the MLC1 gene are the main cause of the disease.

Megalencephalic leukoencephalopathy with cysts without MLC1 defect.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disease characterized by early infantile macrocephaly and delayed motor and cognitive deterioration. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen cerebral white matter and subcortical cysts. On follow-up, atrophy ensues.