Table 4.

Types of FMR1 Repeat Expansion Pathogenic Variants

Variant TypeNumber of CGG Trinucleotide RepeatsMethylation Status of FMR1Clinical Status
Premutation~55-200UnmethylatedAt risk for FXTAS 1At risk for POI and FXTAS 1
Full mutation>200Completely methylated100% with MR~50% with ID, ~50% normal intellect
Repeat size mosaicismVaries between premutation and full mutation in different cell linesPartial: unmethylated in the premutation cell line; methylated in the full-mutation cell lineNearly 100% affected with ID; may be higher functioning 2 than males with full mutationHighly variable: ranges from normal intellect to affected
Methylation mosaicism>200Partial: mixture of methylated and unmethylated cell lines
Unmethylated full mutation>200UnmethylatedNearly all have ID but often have high-functioning MR to low-normal intellect

ID=intellectual disability


Both males and females with premutations and manifestations of some symptoms of fragile X syndrome have been reported [Riddle et al 1998, Bourgeois et al 2009, Hunter et al 2009, Chonchaiya et al 2010].


FMR1 pathogenic variants are complex alterations involving non-classic gene-inactivating variants (trinucleotide repeat expansion) and abnormal gene methylation. This complexity at the gene level affects production of the FMR1 protein and may result in an atypical presentation in which affected individuals occasionally have an IQ above 70, the traditional demarcation denoting intellectual disability (previously referred to as mental retardation).

From: FMR1-Related Disorders

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