Gene Discovery Advances Understanding of Neurological DisordersExperts Will Apply This to Treatment Studies< April 29, 2003 >The identification of the gene responsible for two related, inherited neurological disorders was announced this week by scientists at the National Human Genome Research Institute (NHGRI) and the National Institute of Neurological Disorders and Stroke (NINDS), both of the National Institutes of Health (NIH). And, the scientists found a direct link in this gene and its enzyme product in a human genetic disease, according to a report in the American Journal of Human Genetics. Called GARS (glycyl tRNA synthetase), the gene found by NHGRI and NINDS scientists is responsible for Charcot-Marie-Tooth (CMT) disease type 2D and distal spinal muscular atrophy (dSMA) type V. CMT Disease Affects Peripheral NervesCMT represents a group of genetic diseases that causes muscle weakness and wasting, or atrophy, in the feet, legs, hands, and forearms, as well as diminished sensation in the limbs. CMT disease affects the peripheral nerves - the nerves that travel to the muscles of the limbs - and is known as a peripheral neuropathy. Estimated to affect one in 2,500 individuals, it is the most common inherited neurological disorder. Some forms of CMT disease are autosomal dominant, meaning that a person needs to inherit only one defective copy of the responsible gene to acquire the disease. Other forms are autosomal recessive, meaning both copies of the gene must be defective to result in illness. There is also a form of CMT that is X-linked, meaning that the responsible gene is located on the X chromosome, one of the two sex chromosomes. In most cases, CMT disease begins with mild symptoms, typically foot and ankle weakness and fatigue. As atrophy progresses, the patient develops a distinct walk. This is a consequence of muscle weakness in the front of the leg - the feet slap with each step and the body may sway from side to side. Eventually the toes and the fingers curl due to weakness and atrophy in the small muscles of the feet and the hands. Writing and other functions of the hands become difficult. The sensory loss that accompanies the atrophy diminishes an individual's ability to distinguish between hot and cold, and affects the sense of touch. CMT symptoms usually begin in adolescence or early adulthood. There is no cure for the disease, but there are treatment options, including physical therapy and bracing. Life expectancy is usually normal. SMA Affects Spinal Cord Nerve CellsSpinal muscular atrophy (SMA), another of the diseases related to the newly discovered gene, refers to a group of genetic diseases more diverse than those of CMT. SMA is characterized by weakness and wasting of the muscles of the limbs, but the types vary greatly in severity. Most common are autosomal recessive childhood-onset forms that may be fatal. Other types of SMA are inherited in an autosomal dominant fashion. All types of SMA are due to the degeneration of nerve cells within the spinal cord, as opposed to degeneration of the peripheral nerves. The discovery, say the NIH scientists, supports further investigation of this gene family for additional neurological disease genes. They say this research may shed light on a range of disorders, including carpel tunnel syndrome, which affects the hands and the wrists, and the fatal degenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Most people who develop ALS are between the ages of 40 and 70, although the disease can occur at a younger age. "The identification of the defective gene on chromosome 7 responsible for a type of Charcot-Marie-Tooth disease provides another vivid example of how the recently completed human genome sequence is accelerating studies in human genetics," said Dr. Francis S. Collins, director of NHGRI. Finding Brings Hope for Future AdvancesResearchers on the project, including Dr. Kenneth Fischbeck of the NIH, say that this discovery is another piece of a jigsaw puzzle picture of how peripheral nerve diseases and motor neuron diseases happen. "It provides a more complete view of the mechanism of these diseases," he says. "This will hopefully lead to new treatment approaches. The more complete the picture, the more we know how to intervene. "The next step is to explore what it is about motor nerve cells that make them particularly vulnerable to mutations in these genes," said Dr. Fischbeck. Always consult your physician for more information. What Are the Symptoms of Spinal Muscular Atrophy?Spinal muscular atrophy is sometimes difficult to diagnose, as symptoms can resemble other conditions or medical problems. Each person may experience symptoms differently. There are four types of spinal muscular atrophy based on symptoms and age of onset. When diagnosed in childhood, the following symptoms may occur:
Always consult your physician for more information. |
For more information on nervous system disorders, please visit health information modules on this Web site. What Is Genetics?Genetics is the branch of medicine concerned with how hereditary and genetic factors play a role in causing a disease, birth defect, or inherited susceptibility to health problems, such as neurological disorders and cancer. Genes are the blueprints for making the substances, called proteins, our bodies need to develop and work properly. Most genes come in pairs, one of which is inherited from the mother and the other from the father. A mutation is a change in a gene that prevents it from working properly. Mutations in genes are inherited from our biological parents in specific ways. What is autosomal dominant inheritance? Autosomal dominant inheritance means that the gene carrying a mutation is located on one of the autosomes (chromosome pairs 1 through 22). This means that males and females are equally likely to inherit the mutation. "Dominant" means that having a mutation in just one of the two copies of a particular gene is all it takes for a person to have a trait, such as an increased risk of developing cancer. When a parent has a dominant gene mutation, there is a 50 percent chance that any child he/she has will also inherit the mutation. What is autosomal recessive inheritance? Autosomal recessive inheritance means that the gene carrying the mutation is located on one of the autosomes (chromosome pairs 1 through 22). This means that males and females are equally affected. "Recessive" means that both copies of the gene must have a mutation in order for a person to have the trait. One copy of the mutation is inherited from the mother, and one from the father. A person who has only one recessive gene mutation is said to be a "carrier" for the trait or disease, but he/she does not have any health problems from carrying this one mutation. Most people do not know they carry a recessive gene mutation for a disease until they have a child with the disease. Once parents have had a child with a recessive disease, there is a one out of four, or 25 percent chance, with each subsequent pregnancy, for another child to be born with the same disorder. This means that there is a three out of four, or 75 percent chance, for another child to not have the disease. The birth of a child with a recessive condition is often a total surprise to a family, since in most cases, there is no previous family history of the condition. Many autosomal recessive conditions occur this way. It is estimated that all people carry about 20 recessive genes that cause genetic diseases or conditions. It is only when a person has a child with a partner that carries the same recessive gene mutation, that there is a chance of having a child with a recessive condition. Always consult your physician for more information. Online Resources(Our Organization is not responsible for the content of Internet sites.) Centers for Disease Control and Prevention (CDC) Charcot-Marie-Tooth Association Families of Spinal Muscular Atrophy National Institute of Neurological Disorders and Stroke (NINDS), part of NIH National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI), of the National Institutes of Health (NIH) |