基因型-表型关联分析在孤独症谱系障碍早期诊断的研究

Genotype-phenotype analysis in the early diagnosis of autism spectrum disorder

目的探讨表型和基因型分析在孤独症谱系障碍(ASD)早期诊断的临床应用。方法对122名患者进行临床检查和评估,并利用遗传学技术对孤独症患者进行染色体核型分析和分子倒置探针技术(MIP)分析。结果发现1例基因突变患儿,临床表型有典型孤独症症状、严重智力障碍和行为问题、有肌张力低、运动发育落后病史。头颅MRI示胼胝体发育不良和侧脑室轻度增大。9号染色体发生臂间倒位,核型为46,XX,inv(9)(p12q13)。患儿在孤独症易感基因DD3 X3上存在一处杂合框移突变,家系验证结果显示为新发突变。结论 DDX3 X是ASD易感基因,该基因变异会导致神经发育多种功能损害,且存在性别差异。ASD临床表型和遗传基因型的关联研究,为临床预警和早期诊断提供依据。

Objective To discuss the application of phenotype and genotype of patients in the early diagnosis of autism spectrum disorder（ASD）. Methods Physical examination,clinical evaluations were carried out in 122 patients,together by using G-banding karyotype analysis and molecular inversion probe. Results A mutational patient was present with typical autistic symptoms,severe intellectual disability,behavioral problems and the history of hypotonia and motor delay as well as corpus callosum hypoplasia and ventricular enlargement.Ade novo frameshift mutation in the autism-related gene（DDX3 X）was identified in the patient.There was an inverted 9 chromosome and the karyotype designation is 46,XX,inv（9）（p12 q13）. Conclusion The mutations of DDX3 Xare important risk factors of ASD which cause frequently multiple impairments of neurodevelopment and have differential effect by gender.The study of phenotype and genotype will provide important information for early warning and diagnosis in clinical.