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Rett Syndrome Gene Identified

The cause of Rett syndrome has been traced to a specific defective gene located on the X chromosome, according to a report in the October 1999 issue of Nature Genetics. These researchers may not have proved that this gene is the only gene involved, but they are absolutely certain that it is the main gene which is causing Rett syndrome.

Arriving at this finding has been very illusive, and yet, it is considered to be a very important finding since Rett syndrome is one of the more common forms of mental retardation. And it has been almost exclusively seen as affecting females. The syndrome probably affects one out of every 10,000 females in the United States.

This Rett gene itself is now known as MeCP2. The gene controls the cells throughout a person’s body which are involved in regulating the manufacture of a protein known as methyl-CpG-binding protein 2. Thus the gene name, MeCP2. This Rett gene is located on the long arm of the X chromosome in a region assigned with an identification of Xq28.

According to these Baylor and Stanford university researchers, the isolation effort to clearly identify the specific gene from among the thousands of genes located on the long arm of the X chromosome, has been very difficult. For one thing, Rett syndrome occurs sporadically more than 99% of the time.

Rett syndrome is clearly a childhood neuro-developmental disorder. Most cases might be sporadic, but predominantly the cases are female. These young girls are almost always considered to be normal during their first 6 to 18 months of development. Then they begin to gradually deteriorate mentally and physically.

After this early duration of seemingly “normal” development, a period of regression begins to occur. The first notice of deterioration is often marked by the observation of a loss of purposeful hand-use and speech. As the damage to the affected child’s central nervous system worsens, she usually loses her ability to speak, starts to have difficulty walking, and she may even start having seizures. A very significant delay in her physical growth and then the observation of profound mental retardation often follows.

Since the Rett gene lies on the X chromosome, it has been historically confusing why males are not much more affected. These researchers suggest, in their article, that because of differences in the sex chromosomes, (the X chromosome and the Y chromosome), girls apparently can survive with Rett syndrome, while affected males more often die before or shortly after birth.

Their reasoning: Females have two X chromosomes. Only one of their chromosomes is active in any particular cell. As a result, just half of the cells in a female’s nervous system will actually be controlled by any defective gene. In the male’s nervous system, he has only a single X chromosome. Therefore, all of these “male” cells will be controlled by a faulty gene. This occurrence in males often results in a fatal impact.

The ability to diagnose the Rett disorder before a child is four or five years old is quite difficult. This genetic discovery may result in the general capability of discretely testing for Rett syndrome, which would allow professionals to accurately identify the disorder and thereby improve the accuracy of early diagnosis. As this becomes combined with an effective therapy, the test might allow doctors to forestall the drastic consequences of the disease.

(Breaking The Silence in Rett Syndrome; Huntington F. Willard and Brian D. Hendrich; Nature Genetics, volume 23, October 2, 1999)

(Gene today … Gone tomorrow; Huda Zoghbi, Uta Francke, Kathy Hunter; Nature Genetics, volume 23, October 2, 1999)