June 8, 2010
MUMBAI: New research by a team of Bangalore-based scientists has given hope to those with emotional problems caused by the inheritance of a fragile X chromosome. The researchers, for the first time in the world, mapped defective connections between nerve cells in the emotional hub of the brain of mice who had Fragile X Syndrome. The research has just been published in the online edition of the US-based Proceedings of the National Academy of Sciences.
In humans, while a fragile X chromosome may be passed from one generation to the next with no debilitating effects, the syndrome does affect one in 4,000 men and one in 6,000 women. Upto 20% of boys with autism have the condition due to Fragile X.
The syndrome is the most common inherited cause of intellectual impairment and most common genetic cause of autism. Poor emotional response, hyperactivity, LD and attention deficit are other conditions Fragile X can cause.
The research, by a team from the National Centre for Biological Sciences (NCBS), shows that medication and therapy could reverse the effects of Fragile X. The NCBS team has shown that even the long-term ravages of the condition could be reversed with medication in mice.
Dr Sumantra Chattarji, who heads the NCBS team of neuro-scientists, said the researchers mapped the cellular basis of emotional problems associated with Fragile X, which is a genetic mutation in the X chromosome. "We have identified novel synaptic defects in the amygdala-the emotional hub of the brain," Chattarji said. Synaptic connections are those between two nerve cells.
The team found cellular signalling deficient in cells in the amygdala. Incidentally, this is the second important finding by the NCBS team on Fragile X. In 2007, the same scientists identified a specific enzyme that caused Fragile X. It established that inhibiting the enzyme, called P21-Activated Kinase (PAK), reversed the debilitating symptoms of Fragile X in mice.
This time around, the NCBS scientists, along with their collaborators at New York University, studied the synapses in the amygdala. "Using electro-physiological recordings from cells in the amygdala, my student Aparna Suvrathan identified synaptic defects on both sides of the synapses. Not only is there a shortage of glutamate being released, the receptors available to bind glutamate are also below normal levels," said Chattarji.
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Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited mental retardation in males and a significant cause of mental retardation in females. Family members who have fewer repeats in the FMR1 gene may not have mental retardation, but may have other problems. Women with less severe changes may have premature menopause or difficulty becoming pregnant. Both men and women may have problems with tremors and poor coordination. There is no specific treatment for Fragile X syndrome. Instead, training and education help affected children function at as high a level as possible. Because the condition is not rare, educational approaches have been developed and tested. Fragile X syndrome is caused by a change in the FMR1 gene. A small section of the gene code (three letters only -- CGG) is repeated on a fragile area of the X chromosome. The more repeats, the more likely there is to be a problem. Normally, the FMR1 gene makes a protein needed for your brain to grow properly. A defect in this gene makes your body produce too little of the protein, or none at all. Boys and girls can both be affected, but because boys have only one X chromosome, a single fragile X is likely to affect them more severely. You can have Fragile X syndrome even if your parents do not have it. The person will have a family history of Fragile X syndrome (especially a male relative). There are very few outward signs of Fragile X syndrome in babies. Some signs may include: In females, excess shyness may be the only sign of the problem. A genetic test called polymerase chain reaction (PCR) is used to diagnose this disease. This test looks for a mutation (called a triplet repeat) in the FMR1 gene. In the past, a specific type of chromosome analysis was done. Such testing may still be available. The outcome depends on the extent of mental retardation. Genetic counseling may help both existing and prospective parents with a family history of Fragile X syndrome, or a family history of other symptoms such as tremor. Genetic testing can help determine the level of risk in these families. Accurate diagnosis is important, because other family members can inherit Fragile X syndrome or other problems related to an increased number of repeats in FMR1. Complications vary depending on the type and severity of symptoms. Call your health care provider if you suspect Fragile X syndrome in a child with mental retardation. Genetic counseling is recommended to help families understand the condition, and to understand the complex nature of DNA testing in Fragile X. 