Mak Annisa Shui Lam, Chiu Annie Ting Gee, Leung Gordon Ka Chun, Mak Christopher Chun Yu, Chu Yoyo Wing Yiu, Mok Gary Tsz Kin, Tang Wing Fai, Chan Kelvin Yuen Kwong, Tang Mary Hoi Yin, Lau Yim Elizabeth Tak-Kwong, So Kin Wai, Tao Victoria Qinchen, Fung Cheuk Wing, Wong Virginia Chun Nei, Uddin Mohammed, Lee So Lun, Marshall Christian R, Scherer Stephen W, Kan Anita Sik Yau, Chung Brian Hon Yin
Department of Obstetrics and Gynaecology, Queen Elizabeth Hospital, Hong Kong, Special Administrative Region, China.
Department of Paediatrics & Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Special Administrative Region, China.
Mol Autism. 2017 Jun 26;8:31. doi: 10.1186/s13229-017-0136-x. eCollection 2017.
Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD.
DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature.
Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases.
The duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings.
阵列比较基因组杂交（aCGH）被推荐作为自闭症谱系障碍（ASD）儿童的一线基因检测方法。然而，结果解读往往具有挑战性，部分原因是非欧洲ASD患者的拷贝数变异（CNV）研究不足。为填补这一文献空白，我们报告了一组中国ASD儿童的CNV研究结果。
2011年1月至2014年8月期间，从一家儿童评估中心招募了258名中国ASD患者，并获取其DNA样本。使用NimbleGen-CGX-135k或安捷伦-CGX 60k寡核苷酸阵列进行aCGH检测。结果根据现有指南和文献进行分类。
在9名患者中发现了10个致病性CNV和1个可能致病性CNV，总体诊断率为3.5%。在1名患者（0.39%）中鉴定出一个138 kb的重复，涉及 （arr[GRCh37] 2q14.1(116534689_116672358)x3）的3'外显子，据报道与ASD相关。在DECIPHER数据库中，相同的CNV被报告为意义未明的变异（VUS）。在我们的血统匹配对照中，以及从文献和基因组数据库中，均鉴定出多个携带类似重复的典型发育个体，频率为6/653（0.92%）。
重复可能是一种良性CNV多态性，在中国南方人群中富集，人群频率约为1%。这突出了在解读aCGH结果时使用血统匹配对照的重要性。
