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

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Abstract

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.

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Acknowledgements

We thank all of the families who participated in this project. This work was supported by grants from the National Natural Science Foundation of China (81761128035 and 81781220701), the Shanghai Municipal Science and Technology Committee (17XD1403200 and 18dz2313505), the Research Physician Project of Shanghai Municipal Education Commission (20152234), the Shanghai Municipal Health and Family Planning Commission (GDEK201709, 2017ZZ02026, and 2017EKHWYX-02), and the Scientific Program of Shanghai Shenkang Hospital Development Center (16CR2025B) of China.

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  1. Mingyu Xu and Yiting Ji have contributed equally to this work.

Authors and Affiliations

  1. Developmental 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

    Mingyu Xu, Ting Zhang, Xiaodong Jiang, Yun Fan & Fei Li

  2. Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Yiting Ji

  3. Hangzhou Joingenome Diagnostics, Hangzhou, 311188, China

    Juan Geng

  4. Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Xiaodong Jiang

  5. Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China

    Fei Li

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  1. Mingyu Xu
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Correspondence to Juan Geng or Fei Li.

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Xu, M., Ji, Y., Zhang, T. et al. Clinical Application of Chromosome Microarray Analysis in Han Chinese Children with Neurodevelopmental Disorders. Neurosci. Bull. 34, 981–991 (2018). https://doi.org/10.1007/s12264-018-0238-2

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