Premature ovarian insufficiency caused by FMR1 premutations may be underdiagnosed

Marques, Isabel; Jorge, Paula; Santos, Rosário

http://hdl.handle.net/10400.18/657

Use this identifier to reference this record.

Name:	Description:	Size:	Format:
CursoMRMinho_2011.pdf		649.28 KB	Adobe PDF	Download

Send Feedback

Authors

Marques, Isabel

Jorge, Paula

Santos, Rosário

Abstract(s)

The FMR1 gene [Xq27.3; MIM*309550] has an unstable region comprised of CGG triplets located the 5´untranslated region. Based on the number of those repeats alleles are classified as normal, intermediate, premutation or full mutation, respectively from triplet numbers between 5 to 49, 50 to 58, 59-200 or over 200 CGG triplets. Full mutation-size expansions are associated with the fragile X phenotype. The Fragile X Syndrome [FXS; MIM#300624] is the most common cause of inherited intellectual disability. In contrast, Premutation carriers do not have manifestations of FXS in cognitive deficits, but are at increased risk for development of the ‘‘Fragile X–associated disorders'’. Examples are the Fragile X tremor ataxia syndrome [FXTAS; MIM#300623] and Fragile X Primary Ovarian Insufficiency [FXPOI; MIM#311360] (Figure 1). The FXTAS affects predominantly older males and includes gait ataxia, intention tremor and cognitive impairment, FXPOI affects approximately 20% of females with FMR1 premutations and is characterized by onset of menopause before age 40. Interestingly, the repeat size alleles that have the highest risk of developing FXPOI are in the range of 80-99 CGGs and result in a reduction of 7 years in the menopause appearance. Studies show that women who have idiopathic POI have a 1/50 chance of being a FMR1 carrier, whereas affected women with a family history of POI, have a 1/15 chance of carrying this premutation [1, 2, 3].