AFF2 Repeat Expansion Testing

Description

Pathogenic CGG repeat expansions in the 5’UTR of the AFF2 gene have been associated with X-linked FRAXE intellectual disability syndrome, also known as intellectual developmental disorder, type 109. The pathogenic repeat expansions can lead to methylation of the region and subsequent silencing of AFF2 expression.

Pathogenicity is dependent upon CGG repeat length according to the following ranges 1-3:

Normal Alleles

Mutable Normal Alleles

Intermediate or Uncertain Alleles

Reduced Penetrance Alleles

Full Penetrance Alleles

6-30

31-60*

61-200*

-

201 or more

*Though not considered pathogenic due to limited evidence, some studies have reported intermediate and premutation range expansions in individuals with FRAXE-related conditions 4.

Alleles in the intermediate, premutation and full mutation ranges can either expand or contract during transmission to offspring.