Giant Axonal Neuropathy
Return to Library
What is giant axonal neuropathy?
Giant axonal neuropathy is an inherited condition that causes disorganization of a specific type of protein filaments in nerve cells (neurons). The proteins, called neurofilaments, form a structural framework that helps to define the shape and size of the neurons and is essential for normal nerve function.
Giant axonal neuropathy generally appears in infancy or early childhood, and slowly progresses as more cells become involved. Signs of giant axonal neuropathy usually begin in the peripheral nervous system, which controls the arms, legs and many other areas of the body. Most individuals with this disorder first have problems with walking. Later they may lose sensation, coordination, strength, and reflexes in their limbs. Hearing or vision problems may also occur. Extremely kinky hair is characteristic of giant axonal neuropathy, appearing in almost all affected people.
As the disorder progresses, the brain and spinal cord (central nervous system) become involved. This may cause a gradual decline in mental function, loss of control of body movement, and seizures.
How common is giant axonal neuropathy?
Giant axonal neuropathy is a rare disorder; the incidence is unknown.
What genes are related to giant axonal neuropathy?
Mutations in the GAN gene cause giant axonal neuropathy.
Giant axonal neuropathy is caused by mutations in the GAN gene, which provides instructions for making a protein called gigaxonin. Some GAN mutations affect the shape of the protein, changing how it binds to others in organizing the structure of the neuron. Other mutations result in the absence of any functional gigaxonin protein.
Neurons affected by a mutated GAN gene accumulate excess neurofilaments in the axon, the long extension from the nerve cell that transmits its signal to other nerve cells and to muscles. These distended or giant axons do not transmit signals properly and eventually deteriorate, resulting in problems with movement and other nervous system functions.
How do people inherit giant axonal neuropathy?
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.
Source: National Institutes of Health
Research conducted at National Institutes of Health has updated our knowledge about genetics & genomics
2009 AUG 3 - (NewsRx.com) -- "Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP," investigators in the United States report. "Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G -> A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch Subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy," wrote J.S. Friedman and colleagues, National Institutes of Health. The researchers concluded: "Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.." Friedman and colleagues published their study in American Journal of Human Genetics (Mutations in a BTB-Kelch Protein, KLHL7, Cause Autosomal-Dominant Retinitis Pigmentosa. American Journal of Human Genetics, 2009;84(6):792-800). For additional information, contact A. Swaroop, NEI, Neurobiology Neurodegenerat & Repair Laboratory, National Institutes of Health, Bethesda, MD 20892, USA. The publisher of the American Journal of Human Genetics can be contacted at: Cell Press, 600 Technology Square, 5TH Floor, Cambridge, MA 02139, USA. Keywords: United States, Bethesda, Genetics & Genomics, Genetics, Mental Health, Neurodegenerative, Neurodegenerative Disease, Ophthalmology, Retinitis Pigmentosa, Retinopathy, National Institutes of Health. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2009, Pain & Central Nervous System Week via NewsRx.com.
|
