Fragile X Syndrome    This page contains tooltip text

Fragile X syndrome is the leading inherited form of cognitive impairment (formerly referred to as mental impairment or retardation), affecting nearly one person in 3,000 worldwide. It is also the leading single gene associated with autism. Approximately 2-6% of cases of autism are associated with fragile X syndrome, and approximately one-third of all boys with fragile X syndrome will meet diagnostic criteria for autism, with a larger number meeting criteria for autism spectrum disorders (ASD).

Although often referred to as a form of "intellectual disability", fragile X syndrome is a much broader spectrum disorder that includes learning disabilities and emotional problems; behavioral difficulties; and relatively mild physical features including prominent ears, high arched palette, hyperextensible joints, and macroorchidism.

Fragile X syndrome is caused by large expansions of a three nucleotide (C·G·G) repeat within the fragile X (fragile X mental retardation 1; FMR1) gene [OMIM +309550]. For expansions of more than about 200 repeats, the gene generally becomes silent. In the absence of the FMR1 protein (FMRP), brain development - the ability to form the proper neural connections accompanying learning - is impaired.

Our laboratory is currently studying how the FMR1 gene is regulated with the long-term goal of developing new approaches for treating fragile X syndrome. We believe that small molecules, including modified DNA and RNA species, that can be targeted to the fragile X gene or its message (RNA) will prove to be effective agents for the treatment of fragile X.

 

Autism and autism spectrum disorders (ASD)
Autism is a behavioral diagnosis based on the degree of severity of three core features: impairment of social interactions, absence or delayed language development, and stereotypic behaviors. Individuals not meeting the formal requirements for autism, but who have some of its features, are said to be on the autism spectrum (ASD). Those with Asperger syndrome have impaired social interactions but generally will have good verbal ability; individuals with pervasive developmental disability, not otherwise specified (PDD-NOS) may have impairments in all three domains, but not meeting the degree of impairment required for a diagnosis of autism.

Silent
Gene silencing refers to a process whereby the gene ceases to produce mRNA and therefore does not produce any of its protein product. For more details, go to the "Anatomy of a Gene" page.

Macroorchidism
Increased testicular volume, generally occurring after puberty.

FMRP
The fragile X mental retardation 1 (FMR1) protein, FMRP, is an RNA binding protein that is believed to regulate the translation of many other RNAs, including those RNAs that are important for the normal development and functioning of the synaptic connections in the brain. The "mGluR" theory of fragile X is based on the proposal that the absence of FMRP in fragile X syndrome results in the overactivity of the mGluR pathway, and that blocking the mGluR 5 receptor will improve intellectual functioning.