title: The fragile site WWOX gene and the developing brain.
abstract: WWOX was cloned as a tumor suppressor gene mapping to chromosomal fragile site FRA16D. Loss of WWOX is closely related to tumorigenesis, cancer progression, and therapy resistance. Recent studies demonstrate the growing role of WWOX gene in other human pathologies such as metabolic and nervous system-related conditions. The neurologic phenotype of WWOX mutation includes seizures, ataxia, developmental delay, and spasticity of variable severity. WWOX is a ubiquitous protein with high expression in many tissues including brain, cerebellum, brain stem, and spinal cord. WWOX is highly expressed in different brain regions during murine fetal development and remained unchanged in the cortex and the corpus callosum in adult mice. The mechanism or the putative role of WWOX in the nervous system is still unclear but may include abnormal signaling protein, disruption of neuronal pathways, neuronal differentiation, mitochondrial dysfunction, or apoptosis. Homozygous mutations affecting WWOX in humans are likely to be more described in the future using exome sequencing. The described findings highlight that WWOX plays a critical role in normal central nervous system development and disease. The aim of this review is to summarize the roles of WWOX in the developing brain.
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Prince Sultan Military Medical City, 11159 Riyadh, Saudi Arabia bmelaiki@psmmc.med.sa.
authors.forename: Brahim
authors.initials: B
authors.lastname: Tabarki
authors.affiliation: Division of Metabolic and Genetics, Department of Pediatrics, Prince Sultan Military Medical City, 11159 Riyadh, Saudi Arabia.
authors.forename: Fuad
authors.initials: F
authors.lastname: Al Mutairi
authors.affiliation: Division of Metabolic and Genetics, Department of Pediatrics, Prince Sultan Military Medical City, 11159 Riyadh, Saudi Arabia.
authors.forename: Amal
authors.initials: A
authors.lastname: Al Hashem
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D001927:Brain Diseases / Q000235:genetics / Q000378:metabolism; D043283:Chromosome Fragile Sites / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; C000599481:WWOX protein, rat; C428130:Wwox protein, mouse
keywords: WWOX gene; ataxia; brain; seizures; spasticity