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. 2020 Apr;22(4):758-766.
doi: 10.1038/s41436-019-0733-5. Epub 2020 Jan 3.

Clustering of comorbid conditions among women who carry an FMR1 premutation

Emily Graves Allen  1 , Krista Charen  2 , Heather S Hipp  3 , Lisa Shubeck  2 , Ashima Amin  2 , Weiya He  2 , Jessica Ezzell Hunter  4 , Stephanie L Sherman  2
Affiliations

Clustering of comorbid conditions among women who carry an FMR1 premutation

Emily Graves Allen et al. Genet Med. 2020 Apr.

Abstract

Purpose: Emerging evidence indicates that women who carry an FMR1 premutation can experience complex health profiles beyond the two well-established premutation-associated disorders: fragile X-associated primary ovarian insufficiency (FXPOI, affects ~20-30% carriers) and fragile X-associated tremor-ataxia syndrome (FXTAS, affects ~6-15% carriers).

Methods: To better understand premutation-associated health profiles, we collected self-reported medical histories on 355 carrier women.

Results: Twenty-two health conditions were reported by at least 10% of women. Anxiety, depression, and headaches were reported by more than 30%. The number of comorbid conditions was significantly associated with body mass index (BMI) and history of smoking, but not age. Survival analysis indicated that women with FXPOI had an earlier age at onset for anxiety and osteoporosis than women without FXPOI. Cluster analysis identified eight clusters of women who reported similar patterns of comorbid conditions. The majority of carriers (63%) fell into three categories primarily defined by the presence of only a few conditions. Interestingly, a single cluster defined women with symptoms of FXTAS, and none of these women had FXPOI.

Conclusion: Although some women with a premutation experience complex health outcomes, most carriers report only minimal comorbid conditions. Further, women with symptoms of FXTAS appear to be distinct from women with symptoms of FXPOI.

Keywords: FMR1; FXPOI; FXTAS; fragile X syndrome; premutation.

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Conflict of interest statement

The authors declare no conflicts of interest.

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