Copy Number Variations Found in Patients with a Corpus Callosum Abnormality and Intellectual Disability

J Pediatr. 2017 Jun:185:160-166.e1. doi: 10.1016/j.jpeds.2017.02.023. Epub 2017 Mar 8.


Objective: To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays.

Results: In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes.

Conclusions: Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.

Keywords: CNV; SNP array; agenesis of corpus callosum; chromosomal microarray; corpus callosum; dysgenesis of corpus callosum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Agenesis of Corpus Callosum / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Cycle Proteins / genetics
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosome Duplication
  • Chromosomes, Human, Pair 10
  • Chromosomes, Human, Pair 19
  • Chromosomes, Human, Pair 3
  • Chromosomes, Human, Pair 7
  • Chromosomes, Human, Pair 8
  • DNA Copy Number Variations*
  • Female
  • Hedgehog Proteins / genetics
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Microarray Analysis
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Young Adult
  • Zinc Finger E-box-Binding Homeobox 1 / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • HEY1 protein, human
  • Hedgehog Proteins
  • SHH protein, human
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1