Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Author(s):Show less -

Moreira, Danielle P. ^[1] ; Griesi-Oliveira, Karina ^[1] ; Bossolani-Martins, Ana L. ^[2] ; Lourenco, Naila C. V. ^[1] ; Takahashi, Vanessa N. O. ^[1] ; da Rocha, Katia M. ^[1] ; Moreira, Eloisa S. ^[1] ; Vadasz, Estevao ^[3] ; Castro Meira, Joanna Goes ^[1] ; Bertola, Debora ^{[4, 1]} ; O' Halloran, Eoghan ^[5] ; Magalhaes, Tiago R. ^{[5, 6]} ; Fett-Conte, Agnes C. ^[2] ; Passos-Bueno, Maria Rita ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biociencias, Ctr Pesquisas Genoma Humano & Celulas Tronco, Dept Genet & Biol Evolut, Sao Paulo - Brazil

^[2] Fac Med Sao Jose do Rio Preto, Dept Biol Mol, Sao Jose Do Rio Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Med, Hosp Clin, Inst Psiquiatria, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Inst Crianca, Sao Paulo - Brazil

^[5] Natl Univ Ireland Univ Coll Dublin, Sch Med & Med Sci, Acad Ctr Rare Dis, Dublin 4 - Ireland

^[6] Our Ladys Childrens Hosp, Natl Childrens Res Ctr, Dublin - Ireland

• Document type: Journal article
• Source: PLoS One; v. 9, n. 9 SEP 25 2014.
• Web of Science Citations: 12

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. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 08/57899-7 - Stem cells in human genetic diseases - CETGEN
• Grantee: Mayana Zatz
• Support Opportunities: Research Projects - Thematic Grants