Genome-wide copy number variations analysis in 64 patients with unexplained intellectual disability

Objective To investigate the genetic basis of patients with intellectual disability, and to assess the application of single nucleotide polymorphisms (SNP)-array in the molecular diagnosis of intellectual disability. Methods Sixty-four patients with intellectual disability who were identified in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2013 to June of 2015 were enrolled.Genomic DNA was extracted from peripheral blood and was analyzed with Illumina Humancyto SNP-12 300K gene array chip.All identified copy number variants (CNVs) were analyzed with references from databases such as ClinVar, DECIPHER, OMIM and DGV(Database of Genomic Variants), as well as comprehensive literature review from PubMed database to determine the pathogenicity of CNVs. Results Sixteen cases of the above 64 patients were found to have CNVs with genomic alterations, including 6 cases microdeletions/microduplications associated with known syndromes, 3 cases microdeletions and microduplications with clear clinical relevance (non-syndrome), 1 case numerical chromosome aberration, 1 case unbalanced translocation and 5 cases CNVs of unknown clinical significance.The detection rate was 25% (16/64 cases). Among these 16 abnormalities, 6 cases of them could not be detected by using karyotyping analysis because their sizes were less than 5 Mb, and the smallest detected missing fragment was 0.53 Mb. Conclusion SNP-array gene chip technique with the advantages of higher efficiency, high-resolution and good accuracy, which can be applied to the genetic diagnosis of intellectual disability. Key words: Intellectual disability; Microdeletions/microduplications; Single nucleotide polymorphism arrays