Volume 34, Issue. 6, December, 2018

Clinical Application of Chromosome Microarray Analysis in Han Chinese Children with Neurodevelopmental Disorders

Mingyu Xu1• Yiting Ji2• Ting Zhang1• Xiaodong Jiang1,3• Yun Fan1• Juan Geng4,*• Fei Li5,*

1Developmental and Behavioral Pediatric & Child Primary Care Department, Ministry of Education-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
2Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
3Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China
4Hangzhou Joingenome Diagnostics, Hangzhou 311188, China
5Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China


Chromosome microarray analysis (CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon. We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6% (59 out of 434). This gave a detection rate of 14.7% for developmental delay/intellectual disability (DD/ID, 38/259) and 12% for autism spectrum disorders (ASDs, 21/175). Thirty-three recurrent (n ≥ 2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes (such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes). The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results (94.9%) had benefits, allowing earlier diagnosis (36/59), prioritized full clinical management (28/59), medication changes (7/59), a changed prognosis (30/59), and prenatal genetic counseling (15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential. We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility.


Chromosome microarray analysis; Neurodevelopmental disorder; Autism spectrum disorder; Chromosome syndrome; Clinical management


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