Screening for intellectual disability using high-resolution CMA technology in a retrospective cohort from Central Brazil

PLoS One. 2014 Jul 25;9(7):e103117. doi: 10.1371/journal.pone.0103117. eCollection 2014.

Abstract

Intellectual disability is a complex, variable, and heterogeneous disorder, representing a disabling condition diagnosed worldwide, and the etiologies are multiple and highly heterogeneous. Microscopic chromosomal abnormalities and well-characterized genetic conditions are the most common causes of intellectual disability. Chromosomal Microarray Analysis analyses have made it possible to identify putatively pathogenic copy number variation that could explain the molecular etiology of intellectual disability. The aim of the current study was to identify possible submicroscopic genomic alterations using a high-density chromosomal microarray in a retrospective cohort of patients with otherwise undiagnosable intellectual disabilities referred by doctors from the public health system in Central Brazil. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had intellectual disability and a normal karyotype. The analysis detected 18 CNVs in 60% of patients. Pathogenic CNVs represented about 22%, so it was possible to propose the etiology of intellectual disability for these patients. Likely pathogenic and unknown clinical significance CNVs represented 28% and 50%, respectively. Inherited and de novo CNVs were equally distributed. We report the nature of CNVs in patients from Central Brazil, representing a population not yet screened by microarray technologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brazil
  • Chromosome Aberrations*
  • Chromosomes, Human / genetics*
  • DNA Copy Number Variations / genetics*
  • Female
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Karyotyping
  • Microarray Analysis / methods
  • Middle Aged

Grants and funding

The authors report the following sources of funding: Conselho Nacional de Desenvolvimento Científico e Tecnológico (Rede Pró Centro-Oeste, grant number 564465/2010-0); Fundação de Amparo a Pesquisa no Estado de Goiás (FAPEG); and Capes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.