Analysis pathogenicity of chromosome micro imbalance in children with unexplained mental retardation or development delay

Abstract

Objective To investigate clinically chromosome micro imbalance in children with unexplained mental retardation(MR) or development delay(DD) by using high resolution microarray comparative genomic hybridi-zation(Array-CGH), to identify chromosome micro imbalance which might be associated with MR/DD, and evaluate the effectiveness of Array-CGH in etiological diagnosis of children with unexplained MR/DD. Methods One hundred and twenty-six children with unexplained MR/DD were recruited for this study by Array-CGH to detect chromosome micro imbalance.All chromosome micro imbalances were verified with database of genomic variation(DGV), Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources(DECIPHER) and literature review, to determine if the chromosome micro imbalances found in these children were associated with MR/DD. Results Twenty-eight clinically relevant chromosome micro imbalances were detected among 26 children out of 126 children with unexplained MR/DD.The diagnostic yield for the MR/DD children was 20.6%(26/126 cases). These chromosome micro imbalances were undetectable by chromosome analysis.All MR/DD children with chromosome micro imbalances had face dysmorphism and/or surface, organ dysmorphism.The most common abnormality was Prader-Willi syndrome/Angelman syndrome(3/26 cases, 11.5%), which was followed by DiGeroge syndrome(2/26 cases, 7.6%), Cri-du-chat syndrome(2/26 cases, 7.6%) and 16p11.2 deletion syndrome(2/26 cases, 7.6%). Conclusions Chromosome micro imbalance is one of the most common causes of unexplained MR/DD.Array-CGH can detect disease associated with chromosome micro imbalance as a useful evaluation to help differential diagnosis of children with unexplained MR/DD.Screening for chromosome micro imbalance should be firstly carried out in those MR/DD children with face dysmorphism and/or surface, organ dysmorphism. Key words: Mental retardation/development delay; Chromosome micro imbalance; Pathogenicity; Microarray comparative genomic hybridization