CHD8基因新发突变的孤独症谱系障碍1例报道并文献复习

发布时间：2018-02-10 18:06

本文关键词： 孤独症谱系障碍 CHD基因大头畸形生长过快二代测序技术　出处：《中国循证儿科杂志》2015年03期 　论文类型：期刊论文

【摘要】：目的提高对孤独症谱系障碍(ASD)CHD8基因突变患儿临床表型和基因型的认识。方法回顾性分析1例存在CHD8基因突变的ASD患儿的临床资料,并文献复习。结果 1男,3岁3月龄,头围55.0 cm(4 s),身高107.0 cm(2 s),体重23.5 kg(2 s)。有典型的ASD表现,运动明显落后,有慢性便秘史。2提取患儿及其父母静脉血DNA,以二代高通量测序技术对4 813个临床相关基因的外显子区进行测序,共检测到变异8 982个,经筛选流程筛选ASD相关的EHMT1、PCDH9、NLGN4X的错义突变,CHD8的无义突变(c.307CT,p.Gln103*)有致病可能。Sanger测序显示患儿EHMT1、PCDH9的突变来源于父亲,NLGN4X的突变来源于母亲,患儿父母未发现CHD8的突变。3目前国外共报道了CHD8基因与神经发育障碍有关的15个重要突变;CHD8基因突变患者的临床表型包括ASD表现(87%)、身材高大(86%)、大头畸形(80%)、慢性便秘或间歇性腹泻(80%)、运动落后(67%)和睡眠异常(67%)等,本文病例临床表型与文献报道较为一致。结论 CHD8基因是ASD重要的易感基因;ASD患儿合并大头畸形、生长过快,且有慢性便秘或间歇性腹泻时应考虑CHD8基因突变可能,可行基因检测协助诊断。
[Abstract]:Objective to improve the understanding of the clinical phenotype and genotype of autistic pedigrees disorder ASD CHD8 gene mutation. Methods A case of ASD with CHD8 gene mutation was retrospectively analyzed and the literature was reviewed. Results 1 male was 3 years old and 3 months old. The head circumference is 55.0 cm(4 / s, the height is 107.0 cm(2 / s, and the weight is 23.5 kg(2 / s. The venous DNA of children and their parents with chronic constipation history was extracted. The exon regions of 4 813 clinically related genes were sequenced by the second generation high throughput sequencing technique. A total of 8 982 mutations were detected. A screening procedure was used to screen out the missense mutation of EHMT1, PCDH9, NLGN4X, CHD8, which is associated with ASD. (C. 307CTp.Gln103). Sequencing showed that the mutation of EHMT1 / PCDH9 originated from the father, NLGN4X, from the mother, and Sanger sequencing showed that the mutation of EHMT1 / PCDH9 originates from the mother. The mutation of CHD8 has not been found by parents. 3 at present, 15 important mutations of CHD8 gene related to neurodevelopmental disorders have been reported abroad. The clinical phenotypes of patients with CHD8 gene mutation include ASD manifestations, large head malformation, large head malformation, and chronic stool. Occult or intermittent diarrhea (80), movement backward (67), sleep abnormality (67), etc. Conclusion CHD8 gene is an important susceptibility gene of ASD in children with large head malformation, which grows rapidly, and the possibility of CHD8 gene mutation should be considered in patients with chronic constipation or intermittent diarrhea. Feasible gene detection is helpful for diagnosis.
【作者单位】：中山大学附属第三医院;广州金域医学检验中心;
【基金】：国家重点基础研究发展计划(973计划):2012CB517901
【分类号】：R749.94

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