中文摘要：

目的分析中国汉族人群孤独症谱系障碍核心家系的染色体核型特征,并筛查染色体畸变,探讨患者染色体畸变区域是否存在拷贝数变异和神经发育相关基因,为寻找孤独症谱系障碍的遗传病因提供线索。方法采用G带显色技术并依据人类细胞遗传学国际命名体制（International System for Human Cytogenetic Nomenclature,ISCN）对632个孤独症谱系障碍核心家系（包括632例患者及其健康生物学父母1264名）进行染色体核型分析,并根据各染色体带型特征筛查染色体数目和结构畸变情况。经与细胞遗传学芯片标准化联盟（International Standards for Cytogenomic Arrays,ISCA）数据库和人类亚微观结构基因组变异和疾病表型数据库（Database of genomic variation and Phenotype in Humans using Ensembl Resource,DECIPHER）比对,探讨检出的染色体畸变区域是否可能存在与孤独症谱系障碍和神经发育相关的致病性拷贝数变异和基因。结果共检出携带染色体畸变的患者22例,占患者3.48%（22/632）。其中5例为新生畸变,在患者中检出率为0.79%（5/632）,包括1例重复,1例平衡易位,2例Turner综合征核型,1例21q22区域额外未知来源片段;另外17例染色体畸变为父母遗传,占患者2.69%（17/632）。经数据库比对,检出的染色体1q25和3p24畸变区域可能存在致病性较高的拷贝数变异,并累及TNR、ASTN1、NMNAT2等神经发育相关基因。结论部分孤独症谱系障碍患者存在新生染色体畸变;染色体畸变区域可能存在累及神经发育相关致病基因的拷贝数变异。染色体核型分析可为寻找孤独症谱系障碍的遗传病因提供线索。

英文摘要：

ObjectiveTo detect chromosomal aberrations of autism spectrum disorder（ASD）, we performed karyotypes analyses in 632 ASD trios and then investigated whether copy number variants and neurodevelopment related genes are present in the regions of chromosomal aberrations.MethodsKaryotypes analyses were performed in 632 ASD trios（1896 individuals）. In addition, we investigated whether there were pathogenic copy number variants located in the relevant regions of detected aberrant karyotypes by using the database of the International Standards for Cytogenomic Arrays（ISCA） and the Genomic Variation and Phenotype in Humans using Ensembl Resources（DECIPHER） for ASD patients.Results We detected aberrant results in 22 of 632 patients（3.48%） by karyotypes analyses. Of these 22 aberrant karyotypes, 5 were de novo（0.79%）, including the duplication, the translocation, karyotypes of Turner syndrome and the additional material with unknown origin. Seventeen children affected with autism had aberrant karyotypes inherited from oneof their parents. By using the ISCA and the DECIPHER database, we found that several copy number variants with high pathogenicity were located in 1q25 and 3p24. Further, these copy number variants consisted of several genes related to neurodevelopment such as TNR, ASTN1, and NMNAT2.ConclusionThere are a few de novo chromosomal aberrations in some patients affected with ASD. Copy number variants of several pathogenic neurodevelopmental related genes may exist in the regions of chromosomal aberrations. Karyotypes analyses may be applied to explore the genetic etiology in some patients affected with ASD.