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. 2020 Mar;27(3):590-593.
doi: 10.1111/ene.14146. Epub 2020 Jan 17.

The phenotypical implications of immune dysregulation in fragile X syndrome

K-H Yu  1 , N Palmer  1 , K Fox  2 , L Prock  3 , K D Mandl  1   4 , I S Kohane  1   4 , D Prilutsky  4
Affiliations

The phenotypical implications of immune dysregulation in fragile X syndrome

K-H Yu et al. Eur J Neurol. 2020 Mar.

Abstract

Background and purpose: Immune system dysfunction and inflammatory dysregulation have been shown in several animal models of fragile X syndrome (FXS). However, the phenotypical implications of this dysregulation have not been systematically evaluated in a large patient cohort.

Methods: Five thousand seven hundred thirty-six FXS patients from a nationwide health insurance database were identified and compared to 573 600 age- and sex-matched controls. The phenome-wide association studies codes of FXS patients and those without FXS were compared and the false discovery rate was controlled at 0.05 using the Benjamini-Hochberg procedure.

Results: In addition to the commonly reported comorbidities of FXS, an over-representation of infectious diseases, including otitis media, cellulitis and abscess of fingers or toes, viral enteritis, candidiasis and pneumonia, was discovered. In addition, there was an under-representation of autoimmune disorders in FXS patients.

Conclusions: Our systematic comorbidity analyses identified immunologically-based phenotypes associated with FXS. Our findings align with previous observations of compromised immunity and phagocytic defects in animal models of FXS. These results suggest the importance of immune-related pathways in FXS patients and their relevance to the FMR1 gene.

Keywords: genetic and inherited disorders; intellectual disability; trinucleotide repeat diseases.

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References

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    1. Prilutsky D, Kho AT, Palmer NP, et al. Gene expression analysis in Fmr1 KO mice identifies an immunological signature in brain tissue and mGluR5-related signaling in primary neuronal cultures. Mol Autism 2015; 6: 66.

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