Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in autism spectrum disorder Brazilian individuals with and without epilepsy

PLoS One. 2014 Sep 25;9(9):e107705. doi: 10.1371/journal.pone.0107705. eCollection 2014.

Abstract

Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 and 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity and those at 15q11-q13 and 16p11.2 also show incomplete penetrance. In the present work, through multiplex ligation-dependent probe amplification (MLPA) analysis of 531 ethnically admixed ASD-affected Brazilian individuals, we found that the combined prevalence of the 15q11-q13, 16p11.2 and 22q13 CNVs is 2.1% (11/531). Parental origin could be determined in 8 of the affected individuals, and revealed that 4 of the CNVs represent de novo events. Based on CNV prediction analysis from genome-wide SNP arrays, the size of those CNVs ranged from 206 kb to 2.27 Mb and those at 15q11-q13 were limited to the 15q13.3 region. In addition, this analysis also revealed 6 additional CNVs in 5 out of 11 affected individuals. Finally, we observed that the combined prevalence of CNVs at 15q13.3 and 22q13 in ASD-affected individuals with epilepsy (6.4%) was higher than that in ASD-affected individuals without epilepsy (1.3%; p<0.014). Therefore, our data show that the prevalence of CNVs at 15q13.3, 16p11.2 and 22q13 in Brazilian ASD-affected individuals is comparable to that estimated for ASD-affected individuals of pure or predominant European ancestry. Also, it suggests that the likelihood of a greater number of positive MLPA results might be found for the 15q13.3 and 22q13 regions by prioritizing ASD-affected individuals with epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Base Sequence
  • Brazil
  • Child
  • Child Development Disorders, Pervasive / complications*
  • Child Development Disorders, Pervasive / genetics*
  • Chromosomes, Human / genetics*
  • Chromosomes, Human, Pair 15 / genetics
  • Chromosomes, Human, Pair 16 / genetics
  • Chromosomes, Human, Pair 22 / genetics
  • DNA Copy Number Variations*
  • Epilepsy / complications*
  • Female
  • Genomics
  • Humans
  • Male
  • Pedigree
  • Polymorphism, Single Nucleotide

Grants and funding

Support was provided by FAPESP-INCT - grant number: 2008/57899-7; FAPESP-CEPID - grant number: 2013/08028-1; CNPq [http://www.fapesp.br/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.