In a continuously developing society we are still confronted with intellectual disability (ID) and autism around us with quite a high prevalence. 1 in 88 children is diagnosed with autism spectrum disorder (ASD), while 2-3% of the general population is affected by intellectual disability. These two conditions are often comorbid, with approximately 75% of people with autism having a non-verbal Intelligence Quotient (IQ) in the intellectual disability range (below 70). The causes of both ID and ASD are numerous, either genetic or environmental, but the leading inherited single-gene cause of both afflictions if known to be the Fragile X Syndrome (FXS), with approximately 10% of intellectually disabled and 2-6% of autistic individuals being diagnosed with FXS. This syndrome was initially named Martin-Bell syndrome, after the two doctors who first described an X-linked intellectual disability in multiple male members of a family in 1943. Later it was linked to a “fragile site” on the X chromosome, and the name was changed into “fragile X syndrome” in 1970. Only in 1991 the gene responsible for FXS, the fragile X mental retardation 1 gene (FMR1), was discovered, and from that moment on research flourished. The apparent cause of FXS is a CGG trinucleotide repeat longer than 200 CGG units, which leads to hypermethylation and consequently silencing of the FMR1 gene, resulting in the absence of FMR1’s protein product, the fragile X mental retardation protein (FMRP).

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Erasmus MC Rotterdam, J.E. Jurriaanse Stichting, ZonMW
B.A. Oostra (Ben)
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam