Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge.

Journal Article (Journal Article)

BACKGROUND: The pathogenicity of copy number variations (CNV) in neurodevelopmental disorders is supported by research literature. However, few studies have evaluated the utility and counseling challenges of CNV analysis in clinic. METHODS: We analyzed the findings of CNV studies from a cohort referred for genetics evaluation of autism spectrum disorders (ASD), developmental disability (DD), and intellectual disability (ID). RESULTS: Twenty-two CNV in 21 out of 115 probands are considered to be pathogenic (18.3%). Five CNV are likely pathogenic and 22 CNV are variants of unknown significance (VUS). We have found seven cases with more than two CNV and two with a complex rearrangement of the 22q13.3 Phelan-McDermid syndrome region. We identified a new and de novo 1q21.3 deletion that encompasses SETDB1, a gene encoding methylates histone H3 on lysine-9 (H3K9) methyltransferase, in a case with ASD. CONCLUSION: We provide evidence to support the value of CNV analysis in etiological evaluation of neurodevelopmental disorders in autism genetics clinic. However, interpretation of the clinical significance and counseling families are still challenging because of the variable penetrance and pleotropic expressivity of CNV. In addition, the identification of a 1q21.3 deletion encompassing SETDB1 provides further support for the role of chromatin modifiers in the etiology of ASD.

Full Text

Duke Authors

Cited Authors

  • Xu, Q; Goldstein, J; Wang, P; Gadi, IK; Labreche, H; Rehder, C; Wang, W-P; McConkie, A; Xu, X; Jiang, Y-H

Published Date

  • September 2016

Published In

Volume / Issue

  • 80 / 3

Start / End Page

  • 371 - 381

PubMed ID

  • 27119313

Pubmed Central ID

  • PMC5382808

Electronic International Standard Serial Number (EISSN)

  • 1530-0447

Digital Object Identifier (DOI)

  • 10.1038/pr.2016.101


  • eng

Conference Location

  • United States