With $45,000 in grants from FRAXA Research Foundation over several years, Dr. Miklos Toth of Cornell University studied epigenetics (ie factors other than the gene itself) which can determine symptom severity in Fragile X.
Changes in the epigenetic status of genes have recently been implicated in several neurological and psychiatric diseases. Epigenetic changes such as DNA methylation (at CpG dinucleotides) and secondary histone modifications (i.e. acetylation and methylation) have physiological and behavioral consequences similar to genetic mutations but do not involve changes in the DNA sequence.
In the context of the Fragile X syndrome, epigenetics has been limited to the study of the FMR-1 gene itself because its inactivation by DNA methylation triggers the onset of the disease. Here we hypothesize that epigenetic changes in Fragile X are much more widespread because FMRP-1 is a translational inhibitor and could alter the expression of enzymes responsible for DNA methylation and histone modifications. Also FMRP binds a specific set of RNAs, called miRNAs, that are involved in epigenetic modifications. Therefore, absence of FMRP in Fragile X could lead to genome-wide epigenetic modifications involving many genes with pathogenic roles in the disease. Reversing these epigenetic marks would represent a new strategy in the treatment of Fragile X.
Ji-eun Oh, PhD