The phenotypical implications of immune dysregulation in fragile X syndrome.
genetic and inherited disorders
intellectual disability
trinucleotide repeat diseases
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
17
09
2019
accepted:
19
12
2019
pubmed:
19
1
2020
medline:
25
3
2021
entrez:
19
1
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Substances chimiques
FMR1 protein, human
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
590-593Subventions
Organisme : Boston Children's Hospital
Pays : International
Organisme : Harvard University
Pays : International
Informations de copyright
© 2019 European Academy of Neurology.
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