title: Recurrent copy number variations as risk factors for autism spectrum disorders: analysis of the clinical implications.
abstract: Chromosomal microarray analysis (CMA) is currently considered a first-tier diagnostic assay for the investigation of autism spectrum disorders (ASD), developmental delay and intellectual disability of unknown etiology. High-resolution arrays were utilized for the identification of copy number variations (CNVs) in 195 ASD patients of Greek origin (126 males, 69 females). CMA resulted in the detection of 65 CNVs, excluding the known polymorphic copy number polymorphisms also found in the Database of Genomic Variants, for 51/195 patients (26.1%). Parental DNA testing in 20/51 patients revealed that 17 CNVs were de novo, 6 paternal and 3 of maternal origin. The majority of the 65 CNVs were deletions (66.1%), of which 5 on the X-chromosome while the duplications, of which 7 on the X-chromosome, were rarer (22/65, 33.8%). Fifty-one CNVs from a total of 65, reported for our cohort of ASD patients, were of diagnostic significance and well described in the literature while 14 CNVs (8 losses, 6 gains) were characterized as variants of unknown significance and need further investigation. Among the 51 patients, 39 carried one CNV, 10 carried two CNVs and 2 carried three CNVs. The use of CMA, its clinical validity and utility was assessed.
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Oikonomakis
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: K
authors.initials: K
authors.lastname: Kosma
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Mitrakos
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.|Research Institute for the Study of Genetic and Malignant Diseases in Childhood, "Aghia Sophia" Children's Hospital, Athens, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Sofocleous
authors.affiliation: 1st Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Pervanidou
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Syrmou
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.|Department of Genetics, "Alexandra" University Maternal Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Pampanos
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Psoni
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: H
authors.initials: H
authors.lastname: Fryssira
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.|Research Institute for the Study of Genetic and Malignant Diseases in Childhood, "Aghia Sophia" Children's Hospital, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Kanavakis
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Kitsiou-Tzeli
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Tzetis
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004247:DNA / Q000032:analysis / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D004247:DNA
keywords: autism; autism spectrum disorder; chromosome microarray analysis; copy number variations