title: Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in autism spectrum disorder Brazilian individuals with and without epilepsy.
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.
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Danielle P
authors.initials: DP
authors.lastname: Moreira
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Karina
authors.initials: K
authors.lastname: Griesi-Oliveira
authors.affiliation: Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brasil.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Bossolani-Martins
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Naila C V
authors.initials: NC
authors.lastname: Lourenço
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Vanessa N O
authors.initials: VN
authors.lastname: Takahashi
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Kátia M
authors.initials: KM
authors.lastname: da Rocha
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Eloisa S
authors.initials: ES
authors.lastname: Moreira
authors.affiliation: Instituto de Psiquiatria do Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Estevão
authors.initials: E
authors.lastname: Vadasz
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Joanna Goes Castro
authors.initials: JG
authors.lastname: Meira
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil; Instituto da Criança da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Debora
authors.initials: D
authors.lastname: Bertola
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Eoghan
authors.initials: E
authors.lastname: O'Halloran
authors.affiliation: Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; National Children's Research Centre, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Tiago R
authors.initials: TR
authors.lastname: Magalhães
authors.affiliation: Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brasil.
authors.forename: Agnes C
authors.initials: AC
authors.lastname: Fett-Conte
authors.affiliation: Centro de Pesquisas sobre o Genoma Humano e Células Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D001938:Brazil; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000150:complications* / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D056915:DNA Copy Number Variations; D004827:Epilepsy / Q000150:complications*; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide