Autoimmune disease in mothers with the FMR1 premutation is associated with seizures in their children with fragile X syndrome |
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Authors: | Weerasak Chonchaiya Flora Tassone Paul Ashwood David Hessl Andrea Schneider Luis Campos Danh V Nguyen Randi J Hagerman |
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Institution: | (1) Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health System, 2825 50th Street, Sacramento, CA 95817, USA;(2) Division of Growth and Development, Department of Pediatrics, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand;(3) Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Davis, CA, USA;(4) Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA;(5) Department of Psychiatry and Behavioral Sciences, University of California Davis Health System, Sacramento, CA, USA;(6) Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA, USA;(7) Department of Pediatrics, University of California Davis Health System, Sacramento, CA, USA; |
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Abstract: | An increased prevalence of autoimmune diseases in family members of children with autism spectrum disorders (ASD) has been
previously reported. ASD is also a common problem co-occurring in children with fragile X syndrome (FXS). Why ASD occurs in
some individuals with FXS, but not all, is largely unknown. Furthermore, in premutation carrier mothers, there is an increased
risk for autoimmune diseases. This study compared the rate of ASD and other neurodevelopmental/behavioral problems in 61 children
with FXS born to 41 carrier mothers who had autoimmune disease and in 97 children with FXS of 78 carrier mothers who did not
have autoimmune disease. There were no significant differences in the mean age (9.61 ± 5.59 vs. 9.41 ± 6.31, P = 0.836), cognitive and adaptive functioning in children of mothers with and without autoimmune disease. Among children whose
mothers had autoimmune disease, the odds ratio (OR) for ASD was 1.27 (95% CI 0.62–2.61, P = 0.5115). Interestingly, the OR for seizures and tics was 3.81 (95% CI 1.13–12.86, P = 0.031) and 2.94 (95% CI 1.19–7.24, P = 0.019), respectively, in children of mothers with autoimmune disease compared to children of mothers without autoimmune
disease. In conclusion, autoimmune disease in carrier mothers was not associated with the presence of ASD in their children.
However, seizures and tics were significantly increased in children of mothers with autoimmune disease. This suggests a potential
new mechanism of seizure and tic exacerbation in FXS related to an intergenerational influence from autoimmunity in the carrier
mother. |
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