Medical Investigation of Neurodevelopmental Disorders Institute, University of California Davis Health System, 2825 50th Street, Sacramento, CA 95817, USA.
Hum Genet. 2010 Nov;128(5):539-48. doi: 10.1007/s00439-010-0882-8. Epub 2010 Sep 1.
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.
先前已有报道称，自闭症谱系障碍（ASD）患儿的家庭成员中自身免疫性疾病的患病率增加。脆性 X 综合征（FXS）患儿也常伴有 ASD。为何 FXS 患儿中有些会出现 ASD，而有些不会，目前尚不清楚其原因。此外，在脆性 X 前突变携带者母亲中，自身免疫性疾病的风险增加。本研究比较了 41 名患有自身免疫性疾病的 FXS 患儿的 61 名携带者母亲和 78 名未患有自身免疫性疾病的 FXS 患儿的 97 名携带者母亲所生的儿童的 ASD 发生率和其他神经发育/行为问题。患有和不患有自身免疫性疾病的母亲的孩子的平均年龄（9.61±5.59 与 9.41±6.31，P=0.836）、认知和适应功能均无显著差异。在患有自身免疫性疾病的母亲的孩子中，ASD 的优势比（OR）为 1.27（95%CI 0.62-2.61，P=0.5115）。有趣的是，患有自身免疫性疾病的母亲的孩子中癫痫发作和抽动的 OR 分别为 3.81（95%CI 1.13-12.86，P=0.031）和 2.94（95%CI 1.19-7.24，P=0.019），高于未患有自身免疫性疾病的母亲的孩子。总之，携带者母亲的自身免疫性疾病与她们的孩子是否患有 ASD 无关。然而，患有自身免疫性疾病的母亲的孩子中癫痫发作和抽动的发生率显著增加。这表明 FXS 相关的携带母亲的自身免疫可能通过代际影响成为癫痫发作和抽动恶化的潜在新机制。
