Genome-Wide Copy Number Variation Analysis of Chinese Patients with Intellectual Disability

ABSTRACT: Objective: Intellectual disability (ID) is often sporadic, and its complex etiology can make clinical diagnosis difficult. The aims of this study were to detect genomic copy number variations (CNVs) in Chinese patients with ID, and to analyze the correlation between pathogenic CNVs and clinical phenotypes. Methods: After excluding cases of ID caused by chromosomal aneuploidy, metabolic dysfunction, or environmental factors, we enrolled 60 patients with moderate to severe ID. We performed karyotype and single-nucleotide polymorphism (SNP) array analyses for all patients. Finally, we analyzed the relationship between CNVs and phenotype using CNV databases and genotype-phenotype comparisons. Results: Karyotype analysis showed chromosomal terminal abnormalities in five patients and balanced translocations in two patients. Using SNP array analysis for 60 patients, we detected 87 CNVs in 45 patients, which included 16 pathogenic CNVs in 12 patients with a diagnostic yield of 20.0% (12/60). In one patient, we observed 14 regions of homozygosity > 10 Mb to 266 Mb. We detected a large deletion at 16q22.2 or 3q24q25 in each of two patients, in regions that have not previously been associated with specific syndromes. One case carried a 210-kb deletion at 1q21, including only one coding gene, LPPR4, which may be a candidate gene for the ID phenotype. Conclusions: Use of the genome-wide array screening 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. However, interpretation of CNVs remains a major challenge, which is why we believe that publicly shared data on CNVs and phenotypes can create a rich database of information.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83414 | GEO | 2019/06/15

REPOSITORIES: GEO