Fragile-X Syndrome

Fragile X Syndrome is the leading cause of inherited mental retardation, affecting 1 in 4000 males and 1 in 8000 females, with no differences across race or ethnicity. The cause of Fragile X Syndrome was discovered in 1991, which led to a flourish of research activity and resulted in better understanding of the disorder.

Fragile X results from a repetition in the CGG trinucleotide sequence at Xq27.3 located on the long arm of the X chromosome. This repetition inactivates the FMR1 gene, and results in loss of expression of its gene product known as Fragile X mental retardation protein (FMRP). FMRP is believed to be involved in synaptic remodeling, and is vital for normal brain functioning including adequate learning and memory . Males and females bearing a premutation are unaffected. Male carriers are mentioned to as "normal transmitting" males, and they overtake on the mutation, relatively unchanged in size, to all of their daughters.

The diagnosis of fragile X syndrome was originally founded on the sign of a folate-sensitive fragile location at Xq27.3 (FRAXA) induced in cell heritage under conditions of folate deprivation. Cytogenetic investigation of metaphase disperses demonstrates the presence of the fragile location in less than 60% of cells in most influenced individuals. The cytogenetic check has limitations, particularly in checking for carrier rank, and it exhibits a high degree of variability between persons and laboratories.

In 1991, the fragile X gene (FMR1) was distinuished and discovered to comprise a tandemly repeated trinucleotide sequence (COG) near its 5' end. The mutation responsible for fragile X syndrome engages expansion of this replicate segment. The number of CGG repeats in the FMR1 genes of the usual population varies from six to roughly 50. There are two major categories of mutation, premutations of approximately 50 to 200 repeats and full mutations of ...