What molecular abnormality is primarily responsible for Fragile X syndrome?

Fragile X syndrome is primarily caused by a trinucleotide repeat expansion in the FMR1 gene located on the X chromosome. In individuals with this condition, a specific sequence of DNA, which consists of the nucleotides cytosine (C), guanine (G), and adenine (A), is repeated excessively. In typical individuals, this repeat can range from 5 to 44 times, but in those affected by Fragile X syndrome, it can expand to over 200 repetitions. This expansion leads to the methylation of the FMR1 gene, effectively silencing it and preventing the production of the fragile X mental retardation protein (FMRP), which is essential for normal neurological development.

This mechanism explains the connection between genetic mutation and the clinical manifestations of Fragile X syndrome, such as intellectual disability and various behavioral challenges. Thus, the identification of this trinucleotide repeat expansion as the molecular basis for Fragile X syndrome underscores the interplay between genetic structure and function in the pathology of genetic disorders.