Fragile X

The pre-clinical development program for our test for Fragile X has yielded robust data showing accurate predictive value. Our test is designed to eliminate the need for s Southern Blot step thus reducing the time and cost of screening for Fragile X in males. Optimization for transitioning from the pre-clinical to the clinical stage is underway with funding from a grant to the Company from the NIH. A provisional patent for this test was filed with the US PTO in April 2009.

It is the most common hereditary cause of mental impairment in men and a major cause of infertility among women. According to the National Fragile X Foundation, FRAX is present in 1:3600 males and 1:4000 to 1:6000 females. Fragile X Syndrome may result in:

Mental impairment, ranging from learning disabilities to mental retardation
Attention deficit and hyperactivity
Anxiety and unstable mood
Autistic behaviors
Long face, large ears, flat feet
Hyper extensible joints, especially fingers
Seizures (epilepsy)

Fragile X is caused by the expansion of a CGG trinucleotide repeat of the 5' untranslated region (UTR) of the FMR1 gene located on chromosome Xq27.3. Among people without the Fragile X mutation, the number of these "CGG repeats" varies from 6 to about 40. Expansions with 55 and 200 repeats, called permutations, are seen in unaffected carriers; between 40 and 55 repeats is considered a "grey zone" where normal and permutation size ranges overlap. Expansions with more than 200 repeats, called full mutations, are associated with methylation which "turns off" the gene.

Males with a full mutation have Fragile X Syndrome. The majority of males with Fragile X Syndrome will have a significant intellectual disability ranging from learning disabilities to severe mental retardation and autism. In addition, males with FRAX have a variety of physical and behavioral characteristics.

Approximately 50% of females with a full mutation have cognitive impairment, and of the 50% with a normal IQ, 60% have some emotional or behavioral effects. While approximately 1% of women in the general population will
experience premature ovarian dysfunction, studies have shown that women who carry a permutation for Fragile X have a 14% to 16% risk of developing premature ovarian failure. Approximately 1 in 246 to 1 in 468 women carry a Fragile X permutation. An FMR1 permutation tends to increase in size when transmitted from a female to her children, and the risk for expansion to a full mutation increases with the size of the permutation.

Boys are typically more severely affected than girls. While most boys have mental retardation, only one-third to one-half of girls have significant intellectual impairment; the rest have either normal IQ or learning
disabilities. Math is often a particular challenge for girls with Fragile X Syndrome. Emotional and behavioral problems are common in both sexes.

About 20% of boys with FRAX meet full criteria for autism. Most boys and some girls have some symptoms of autism, but many tend to be very social and interested in other people. In other X-linked conditions, all males who carry the gene are affected; however, in Fragile X Syndrome, unaffected males can carry the gene in the permutation form and have no related symptoms. Males with the permutation will pass it on to all of their
daughters and none of their sons (they pass their Y chromosome on to their sons).