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Genome-Wide Array Analysis Reveals Novel Genomic Regions and Candidate Gene for Intellectual Disability

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A Correction to this article was published on 21 November 2018

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Abstract

Introduction

Intellectual disability (ID) is often sporadic, and its complex etiology makes clinical diagnosis extremely difficult.

Objective

The aims of this study were to detect copy number variations (CNVs) in patients with ID and to analyze the correlation between pathogenic CNVs and clinical phenotype.

Methods

After cases of ID caused by metabolic dysfunction or environmental factors were excluded, 64 patients with moderate to severe ID were enrolled. Karyotype and single nucleotide polymorphism (SNP) array analyses were performed for all patients. The relationship between CNVs and phenotype was identified with genotype–phenotype comparisons and by searching CNV databases.

Results

Karyotype analysis showed four patients with chromosomal aneuploidy and seven with chromosomal structural abnormality. After excluding the four cases with chromosomal aneuploidy, the remaining 60 cases were analyzed using SNP array. The results revealed 87 CNVs in 45 cases, including 16 pathogenic CNVs in 12 individuals, with a diagnostic yield of 20.0% (12/60). We found large deletions at 16q22.2q23.1 and 3q24q25.32 in two patients, respectively, in whom specific syndromes had not been defined. Our array analysis showed one case carried a 210 kb deletion at 1p21.2p21.3, which included only one coding gene LPPR4, which might be a candidate gene for ID phenotype.

Conclusions

Use of the genome-wide array method can improve the detection rate of CNVs, reveal chromosomal abnormalities that have not been well-characterized by cytology, and provide a new way to locate genes for patients with the ID phenotype. Interpretation of CNVs remains a major challenge. Sharing of CNVs and phenotype information from different laboratories in public databases is important.

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Change history

  • 21 November 2018

    An Online First version of this article was made available online.

  • 21 November 2018

    An Online First version of this article was made available online.

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Acknowledgements

The authors thank the Genetic Counselling Clinic of Wenzhou Central Hospital for collecting patients’ phenotype information and Prof. Taosheng Huang from Cincinnati Children’s Hospital for revising this manuscript.

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Author notes

  1. Xiangnan Chen and Huanzheng Li contributed equally to this paper.

Authors and Affiliations

  1. Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

    Xiangnan Chen, Lili Zhou & Shaohua Tang

  2. The Center of Wenzhou Prenatal Diagnostics, Key Laboratory of Birth Defects, Wenzhou Central Hospital, Wenzhou, Zhejiang, China

    Huanzheng Li, Chong Chen, Lili Zhou, Xueqin Xu, Yanbao Xiang & Shaohua Tang

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  1. Xiangnan Chen
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Contributions

ST initiated the study, coordinated clinical analyses of patients, and revised the manuscript. XC performed SNP array analyses and Q-PCR, and wrote the manuscript. HL and CC contributed to data collection and processing. XX helped write parts of the manuscript. LZ and YX performed cytogenetic analyses and cytogenetic diagnoses. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Shaohua Tang.

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Conflict of interest

Xiangnan Chen, Huanzheng Li, Chong Chen, Lili Zhou, Xueqin Xu, Yanbao Xiang and Shaohua Tang have no conflicts of interest.

Funding

This study was funded by Wenzhou public technology and medical projects (Y20140655, Y20170207), Wenzhou technology bureau projects (ZD201302).

Informed Consent

Parents or guardians of the probands signed their written informed consent, which were approved by Dingli Clinical School Ethics Committee of Wenzhou Medical University.

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Chen, X., Li, H., Chen, C. et al. Genome-Wide Array Analysis Reveals Novel Genomic Regions and Candidate Gene for Intellectual Disability. Mol Diagn Ther 22, 749–757 (2018). https://doi.org/10.1007/s40291-018-0358-4

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