Just One Gene

Drs. Ben Oostra, Stephen Warren, and David Nelson discovered the gene for Fragile X. FRAXA is the name they gave the mutation which causes Fragile X

In 1991, scientists discovered the gene (called FMR1 for "Fragile X Mental Retardation - 1") that causes fragile X. In people with Fragile X, a defect in FMR1 (a "full mutation") shuts the gene down. Like a defective factory, FMR1 cannot manufacture the protein that it normally makes.

Other individuals are carriers: they have a small defect in FMR1 (called a "premutation") but do not show symptoms.

Fragile X is inherited. Carrier men pass the premutation to all their daughters but none of their sons. Each child of a carrier woman has a 50% chance of inheriting the gene defect. The Fragile X premutation can be passed silently down through generations in a family before a child is affected by the syndrome.

The Fragile X Gene

The FMR1 gene is located on the long arm of the X chromosome. At the start of this gene lies a region of DNA which varies in length from one person to another. Ordinarily, this stretch of DNA falls within a range of length that would be considered "normal".

In some people, however, this stretch of DNA is somewhat longer; this gene change is called a "premutation". Although a person who carries the premutation does not typically have symptoms of Fragile X, the stretch of DNA is prone to further expansion when it is passed from a woman to her children. When the stretch of DNA expands beyond a certain length, the gene is switched off and does not produce the protein that it is normally makes. This gene change is called a "full mutation".

A male who inherits a full mutation exhibits Fragile X syndrome because his only X chromosome contains the mutated gene. A female may not be as severely affected because each cell of her body needs to use only one of its two X chromosomes and randomly inactivates the other.

How is Fragile X inherited?

Each cell in the body contains forty-six (twenty-three pairs of) chromosomes. These chromosomes consist of genetic material (DNA) necessary for the production of proteins which lead to growth, development and physical and intellectual characteristics.

The first twenty-two pairs of chromosomes are the same in males and females. The remaining two chromosomes, X and Y, determine whether a person is male or female.

Males have only one X chromosome which is inherited from the mother. They receive a Y chromosome from the father. Females inherit two X chromosomes, one from each parent.

How common is Fragile X?

Fragile X syndrome is the most common inherited cause of mental impairment and the most common known cause of autism. Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups (source CDC). About 1 in 259 women carry fragile X and could pass it to their children. About 1 in 800 men carry fragile X; their daughters will also be carriers.

Large-scale population studies of fragile X still need to be done, but it is clear that this is one of the most common genetic diseases in humans. Most people with fragile X are not yet correctly diagnosed.

Testing for Fragile X