FMR1 Repeat Expansion Testing

Description

Pathogenic CGG repeat expansions in the FMR1 gene have been associated with X-linked fragile X syndrome (FXS), manifested primarily and more severely in males. Premutation alleles have been associated with increased risk for Fragile X-associated tremor/ataxia syndrome (FXTAS). Full expansion alleles are associated with aberrant hypermethylation of the CGG expansion resulting in the decrease or silencing of FMR1 transcription and the subsequent loss of encoded FMRP protein. The absence of FMRP appears to disrupt neurotransmission mediated by the metabotropic glutamate receptor (mGluR). Premutation alleles, on the other hand, are thought to cause increased levels of FMR1 mRNA which can form toxic inclusions ¹.

Pathogenicity is dependent upon CGG repeat length according to the following ranges ^2-4:

*Females with premutation alleles are at increased risk of having children with FXS.