Prenatal Fragile X testing

The most common inherited cause of mental retardation affecting
approximately 1 in 4000–6000 males and 1 in 8000–10,000 females.
The syndrome is associated with an abnormality of the
Fragile X Mental Retardation 1 (FMR1) gene located at a fragile site on Xq27.3. This alteration results from an unstable expansion of CGG trinucleotide repeats within the 5′ untranslated region of the FMR1 gene.
Normal individuals have
approximately 5 to 40 CGG repeats, while carriers of FXS have 55 to 200 CGG repeats,
which is classified
as a premutation. It is associated with pathological conditions such as premature ovarian failure
in females and fragile X-associated tremor/ataxia syndrome (FXTAS) in males.
FXS is also characterized by a full CGG mutation and
methylation of the cytosine bases, which leads to transcriptional silencing and abnormal levels or an absence of the encoded fragile
X mental retardation protein (FMRP). FMRP is a major protein regulator of the translation of many mRNAs involved in
synaptic plasticity. Since the mutation is X-linked, males are more severely affected than females, and males with FXS
predominantly exhibit mental retardation, autism, and behavioral changes. FXS inheritance depends on the number of
CGG repeats within the promoter of the FMR1 gene. The transition from a premutation to a full mutational
allele can occur
due to expansion during the transmission of the maternal X chromosome, and rarely the paternal X
chromosome, carrying a premutation allele to offspring (1-3).