Genomic copy number variations in three independent neonates with 5p partial monosomy

Objective To screen for genomic copy number variants(CNVs)in three independent neonates with 5p partial monosomy using SNP array,identify the relationship between rare CNVs and related phenotypes.Methods Genomic CNVs were dected in the 3 individuals by using cytogenetic whole-genome 2.7M array.Rare CNVs with potential clinical significance were selected for screening the occurence of deletion and its size in region of 50 kb and duplication region that over 150 kb in chromosome 5 p based on the analysis of ChAs software.Postive CNVs and segment of normal reference populatino were excluded.The identified CNVs were analyzed with the references from CNVs database and published literatures.Results Eleven rare CNVs(12.9%)sized from 66-31 328 kb were identified in the 3 neonates.The deletion region and size were 5p15.33-p13.3 and 31 866 kb for case 1,5p15.33-p15.1 and 15 552 kb for case 2,5p15.33-p14.3 and 19 312 kb for case 3.Additional duplication ons 9p24.3-p21.1 were found in case 2 and 7p22.3-p22.2 were found in case 3.Analysis of the association between phenotype and genotype of 3 cases and 5 patients in database suggested that the overlapping region of abnormal cry and voice was located within a 3.86 Mb region on 5p15.33-p15.31 and contained IRX1 and IRX2 genes.The overlapping region of facial dysmorphology was located within a 2.51 Mb region on 5p15.2-p15.1 and contained ANKH gene.Case 3 has Hirschsprung's disease.Conclusions The study established the methology to discover whole genome CNVs in identifying novel submicroscopic deletions and duplications that can not be detected using G-banding cytogenetic technology,allowing an early diagnosis of affected individuals especially neonates without characteristic symptoms.The results allow us to refine the genotype-phenotype correlations for abnormal cry and voice,facial dysmorphology in 5p partial monosomy.