myelin-basic-protein and Mitochondrial-Diseases

WW domain-containing oxidoreductase (Wwox) is a putative tumor suppressor. Several germline mutations of Wwox have been associated with infant neurological disorders characterized by epilepsy, growth retardation, and early death. Less is known, however, about the pathological link between Wwox mutations and these disorders or the physiological role of Wwox in brain development. In this study, we examined age-related expression and histological localization of Wwox in forebrains as well as the effects of loss of function mutations in the Wwox gene in the immature cortex of a rat model of lethal dwarfism with epilepsy (

Topics: 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; Adenomatous Polyposis Coli Protein; Amino Acid Transport Systems, Acidic; Animals; Antiporters; Astrocytes; Cell Count; Cerebral Cortex; Disease Models, Animal; Dwarfism; Epilepsy; Gene Expression Regulation, Developmental; Germ-Line Mutation; Glial Fibrillary Acidic Protein; Hereditary Central Nervous System Demyelinating Diseases; Male; Mitochondrial Diseases; Myelin Basic Protein; Neurogenesis; Neurons; Oligodendroglia; Prosencephalon; Psychomotor Disorders; Rats; Rats, Transgenic; Signal Transduction; Tumor Suppressor Proteins; WW Domain-Containing Oxidoreductase

4H leukodystrophy is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. With its variability in clinical symptoms, application of pattern recognition to identify specific magnetic resonance imaging (MRI) features proved useful for the diagnosis. We collected 3T MR imaging data of 12 patients with mutations in

Topics: Adolescent; Adult; Brain; Child; Child, Preschool; Female; Hereditary Central Nervous System Demyelinating Diseases; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Mitochondrial Diseases; Myelin Basic Protein; Myelin Proteolipid Protein; Protein Subunits; RNA Polymerase III; Spinal Cord; Young Adult

To evaluate the neurochemical changes associated with hypomyelination, especially to clarify whether increased total N-acetylaspartate (tNAA) with decreased choline (Cho) observed in the thalamus of msd mice with the plp1 mutation is a common finding for hypomyelinating disorders.. We performed magnetic resonance imaging (MRI) and proton MR spectroscopy ((1) H-MRS) of the thalamus and cortex of postnatal 12-week shiverer mice devoid of myelin basic protein (mbp), heterozygous and wild-type mice with a 7.0T magnet. Luxol Fast Blue staining and immunohistochemical analysis with anti-Mbp, Gfap, Olig2, and NeuN antibodies were also performed.. In the thalamus, decreased Cho and normal tNAA were observed in shiverer mice. In the cortex, tNAA, Cho, and glutamate were decreased in shiverer mice. Histological and immunohistochemical analysis of shiverer mice brains revealed hypomyelination in the thalamus, white matter, and cortex; astrogliosis and an increased number of total oligodendrocytes in the white matter; and a decreased number of neurons in the cortex.. The reduction of Cho on (1) H-MRS might be a common marker for hypomyelinating disorders. A normal tNAA level in the thalamus of shiverer mice might be explained by the presence of mature oligodendrocytes, which enable neuron-to-oligodendrocyte NAA transport or NAA catabolism.

Topics: Amino Acid Transport Systems, Acidic; Analysis of Variance; Animals; Antiporters; Aspartic Acid; Brain; Cerebral Cortex; Choline; Disease Models, Animal; Hereditary Central Nervous System Demyelinating Diseases; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred ICR; Mice, Neurologic Mutants; Mitochondrial Diseases; Myelin Basic Protein; Neurochemistry; Psychomotor Disorders; Thalamus; White Matter

To describe a child with apparent brain biopsy-confirmed acute disseminated encephalomyelitis (ADEM) but genetic confirmation of compound heterozygosity for DNA mutations of the polymerase gamma (POLG) gene.. Case report.. Tertiary referral center.. A 4-year-old boy presented with ataxia and encephalopathy.. Magnetic resonance imaging demonstrated multiple focal areas of T2 prolongation. The patient's family refused steroid treatment. His symptoms improved then progressed. Magnetic resonance imaging findings also progressed. A cerebrospinal fluid specimen revealed myelin basic protein and oligoclonal bands. A brain biopsy specimen demonstrated demyelination, suggesting progression of ADEM. However, polymerase chain reaction amplification and sequencing revealed 2 heterozygous mutations of the POLG gene, suggesting mitochondrial disease. The patient died 9 months after his initial presentation.. This case raises interesting questions about whether ADEM triggered severe neurologic degeneration in a patient with mitochondrial disease, whether mitochondrial disease predisposed to a pathologic immune response, or whether mitochondrial disease can mimic an autoimmune disease. Mitochondrial disease-causing mutations may help explain the poor outcome in some cases of apparent autoimmune central nervous system disease.

Topics: Brain; Child, Preschool; Demyelinating Autoimmune Diseases, CNS; Diagnosis, Differential; DNA Mutational Analysis; DNA Polymerase gamma; DNA-Directed DNA Polymerase; Encephalomyelitis, Acute Disseminated; Fatal Outcome; Genetic Markers; Humans; Magnetic Resonance Imaging; Male; Methylprednisolone; Mitochondrial Diseases; Mutation; Myelin Basic Protein; Oligoclonal Bands; Treatment Failure